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1.
Ulf Diekmann Ralf Zarbock Doris Hendig Christiane Szliska Knut Kleesiek Christian G?tting 《Journal of molecular medicine (Berlin, Germany)》2009,87(10):965-970
Pseudoxanthoma elasticum (PXE) is a rare disorder predominantly affecting the skin, the eyes, and the cardiovascular system.
The disease is caused by mutations in the ABCC6 gene and characterized by ectopic calcification and extracellular matrix (ECM) alterations. Matrix metalloproteinases (MMPs)
play a pivotal role in the process of ECM remodeling. In the present study, we investigated matrix metalloproteinases MMP-2
and MMP-9 in PXE patients compared to healthy controls. We analyzed the serum concentrations of MMP-2 and MMP-9 in a cohort
of 69 German PXE patients and in 69 healthy, age-, and sex-matched control subjects using commercially available ELISA assays.
We found elevated concentrations of both MMPs in the sera of PXE patients. MMP-2 levels were significantly higher in patients
than controls (231 ± 5.89 vs 202 ± 5.17 ng/ml, p = 0.0002), as were MMP-9 levels (841 ± 65.9 vs 350 ± 30.8 ng/ml, p < 0.0001). Our findings point to an involvement of matrix metalloproteinases in PXE pathology. ECM remodeling in PXE is reflected
by elevated levels of circulating MMP-2 and MMP-9. Those MMPs might, therefore, be applicable as serum markers for the matrix-degradative
process in PXE. 相似文献
2.
Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma. 总被引:2,自引:0,他引:2
Ville Bister Tiina Skoog Susanna Virolainen Tuula Kiviluoto Pauli Puolakkainen Ulpu Saarialho-Kere 《Modern pathology》2007,20(11):1128-1140
Pancreatic adenocarcinoma is known for early aggressive local invasion, high metastatic potential, and a low 5-year survival rate. Matrix metalloproteinases (MMPs) play important roles in tumor growth and invasion. Earlier studies on pancreatic cancer have found increased expression of certain MMPs to correlate with poorer prognosis, short survival time or presence of metastases. We studied the expression of MMP-21, -26, and tissue inhibitor of matrix metalloproteinases (TIMP)-4 in 50 tissue samples, including 25 adenocarcinomas, seven other malignant pancreatic tumors, and 18 control samples of non-neoplastic pancreatic tissue with immunohistochemistry. The regulation of MMP-21, -26, and TIMP-4 mRNAs by cytokines was studied with RT-PCR in pancreatic cancer cell lines PANC-1, BxPC-3, and AsPC-1. MMP-21, -26, and TIMP-4 were detected in cancer cells in 64, 40, and 60% of tumors, respectively. MMP-21 expressed in well-differentiated cancer cells and occasional fibroblasts, like TIMP-4, tended to diminish in intensity from grade I to grade III tumors. Patients with metastatic lymph nodes had increased expression of MMP-26 in actual tumor samples. All cultured cancer cell lines expressed MMP-21 basally at low levels, and presence of the protein was confirmed immunohistochemically in cultured cells. MMP-21 expression was induced by epidermal growth factor (EGF) in PANC-1 cells. MMP-26 was neither expressed basally nor induced by tumor necrosis factor alpha, transforming growth factor beta-1 (TGFbeta1), EGF, or interferon gamma. Basal TIMP-4 expression was lowest in the poorly differentiated cancer cell line PANC-1 compared to better-differentiated BxPC-3 and AsPC-1 cells. TIMP-4 expression was induced by TGFbeta1 in PANC-1 cells and by EGF in BxPC-3 cells. Our findings suggest that MMP-21 is not a marker of invasiveness, but rather of differentiation, in pancreatic cancer and it may be upregulated by EGF. The putative role of MMP-26 as a marker of metastases warrants further studies. Unlike other TIMPs, TIMP-4 was not upregulated in relation to aggressiveness of pancreatic cancer. 相似文献
3.
Boyd S Tolvanen K Virolainen S Kuivanen T Kyllönen L Saarialho-Kere U 《Virchows Archiv : an international journal of pathology》2008,452(1):83-90
Matrix metalloproteinases (MMPs) have an important role in the initiation, growth, and invasion of malignant tumors. Basal
cell cancer (BCC) is the most common human malignancy. The risk of BCC is 10–16 times higher among organ transplant recipients
compared with the nontransplanted population. The aim of this study was to compare the expression of several MMPs and their
tissue inhibitors (TIMPs) in BCCs from kidney transplant recipients and controls. Expression of MMPs-1, -7, -8, -9, -10, -13,
-26, and TIMPs-1 and -3 was evaluated by immunohistochemistry in 25 samples of BCC of kidney transplant recipients and 25
matched controls representing superficial and nodular subtypes. No significant differences were detected in MMP expression
of BCC tumor cells between immunocompetent and immunodeficient patients. However, MMPs-1 and -9 and TIMP-1 were expressed
more frequently in stromal macrophages in the BCCs of immunocompetent patients. When tumor subtypes were compared irrespective
of the patient group, more MMP-1-positive fibroblasts and MMP-9-positive neutrophils were detected in the superficial subtype,
while stromal MMP-10 expression was more abundant in nodular tumors. Our results suggest that abundant peritumoral expression
of TIMP-1 in non-immunocompromised patients limits ECM degradation permissive for cancer cell migration. 相似文献
4.
5.
Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas. 总被引:2,自引:0,他引:2
Tiina T Kuivanen Leila Jeskanen Lauri Kyll?nen Ulla Impola Ulpu K Saarialho-Kere 《Modern pathology》2006,19(9):1203-1212
Keratoacanthomas are rapidly growing hyperproliferative skin tumors that may clinically or histologically be difficult to distinguish from well-differentiated squamous cell cancers (SCCs). UV light, trauma, and immune suppression represent their etiological factors. As matrix metalloproteinases (MMPs) are implicated at all stages of tumorigenesis, we investigated the expression profile of several cancer-related MMPs to find markers that would differentiate keratoacanthomas from SCCs and shed light to the pathobiology of keratoacanthoma. Samples from 31 keratoacanthomas and 15 grade I SCCs were studied using immunohistochemistry for MMP-2, -7, -8, -9, -10, -13, and -19 and p16 and laminin-5gamma2 chain. In situ hybridization for MMP-7, -10, and -13 was performed in a subset of tumors. Keratinocytes with atypia, presence of neovascularization, and composition of the inflammatory infiltrate were graded from hematoxylin-eosin stainings. MMP-7 was present in the epithelium of 4/31 keratoacanthomas and 9/15 SCCs, MMP-8 in 3/30 keratoacanthomas and 0/15 SCCs, but MMP-13 in 16/31 keratoacanthomas and 10/15 SCCs, and MMP-10 in 28/31 keratoacanthomas and all cancers. MMP-9 was detected in the epithelium in 5/31 keratoacanthomas and 8/15 SCCs, whereas MMP-2 was only present in fibroblasts in both tumors. MMP-19 was upregulated in proliferating epithelium of keratoacanthomas as was p16. Cytoplasmic laminin-5gamma2 was particularly abundant in keratinocytes at the pushing border of MMP-13-positive keratoacanthomas. We conclude that although some MMPs (MMP-10 and -13) are abundantly expressed in keratoacanthomas, the presence of MMP-7 and -9 in their epithelial pushing border is rare and should raise suspicion of SCC. Further, the loss of MMP-19 and p16 could aid in making the differential diagnosis between well-differentiated SCC and keratoacanthoma. Frequent expression of the transformation-specific MMP-13 in keratoacanthomas suggests that they are not benign tumors but incomplete SCCs. 相似文献
6.
Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival 总被引:5,自引:0,他引:5
We have shown recently that the hyaluronan receptor, CD44, and matrix metalloproteinase 9 (MMP-9) form a complex on the surface
of TA/St mouse mammary carcinoma cells that activates latent transforming growth factor-beta (TGF-β) and is required for tumor
invasion. Disruption of the CD44/MMP-9 complex by expression of soluble CD44 results in the loss of tumor invasiveness and
abrogates tumor cell survival in host lung parenchyma following intravenous injection into syngeneic mice. To explore the
molecular nature of the survival signals derived from the CD44/MMP-9 complex during the development of tumor metastasis, we
investigated the possibility that activation of latent TGF-β by the CD44/MMP-9 complex is responsible for tumor cell survival
in host lung parenchyma. TA3 cells overexpressing dominant negative soluble CD44 (TA3sCD44), which compromises native CD44
function and the ability of TA3 cells to develop metastases, were transfected with constitutively active or latent TGF-β2
and tested for their ability to form tumors in syngeneic mice. Our results demonstrate that expression of the constitutively
active, but not the latent, form of TGF-β2 rescues TA3sCD44 cells from apoptosis during lung colonization. These observations
provide evidence that activation of latent TGF-β constitutes an event downstream of CD44-dependent signals that is required
for tumor cell survival and metastatic colony formation. The functional axis composed of CD44, MMP-9 and TGF-β may therefore
play an important role in the metastatic proclivity of selected tumor types. Abbreviations: ECM – extracellular matrix; HA – hyaluronan; HSPG – heparan sulfate proteoglycan; MMP – matrix metalloproteinase; TGF-β–
transforming growth factor β
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
7.
Stojic J Hagemann C Haas S Herbold C Kühnel S Gerngras S Roggendorf W Roosen K Vince GH 《Neuroscience research》2008,60(1):40-49
Glioblastomas (GBM) are the most prevalent type of malignant primary brain tumor in adults. They may manifest de novo or develop from low-grade astrocytomas (LGA) or anaplastic astrocytomas. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, resulting in poor prognosis. Tumor progression is facilitated by an increased activity of proteolytic enzymes such as matrix metalloproteinases (MMPs). Elevated levels of several MMPs were found in glioblastomas compared to LGA and normal brain (NB). However, data for some MMPs, like MMP-1, are controversially discussed and other MMPs like MMP-11 and MMP-19 have as yet not been analysed in detail. We examined the expression of MMP-1, MMP-9, MMP-11 and MMP-19 in NB, LGA and GBM by semiquantitative RT-PCR, Western blotting and immunohistochemistry and found an enhanced expression of these MMPs in GBM compared to LGA or NB in signal strength and in the percentage of tumors displaying MMP expression. The transition from LGA to GBM was characterized by a shift of pro-MMP-11 to expression of the active enzyme. Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy. 相似文献
8.
High levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma 总被引:3,自引:0,他引:3
Davidson B Goldberg I Gotlieb WH Kopolovic J Ben-Baruch G Nesland JM Berner A Bryne M Reich R 《Clinical & experimental metastasis》1999,17(10):799-808
The object of this study was to analyze the potential association between the expression of MMP-2, MMP-9, MT1-MMP and TIMP-2,
and disease outcome in advanced-stage ovarian carcinomas. Sections from 70 paraffin-embedded blocks (36 primary ovarian carcinomas
and 34 metastatic lesions) from 45 patients diagnosed with advanced stage ovarian carcinomas (FIGO stages III–IV) were studied
using mRNA in situ hybridization (ISH) technique. Patients were divided retrospectively in two groups based on disease outcome. Long-term survivors
(21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival
(DFS) and 60 months for overall survival (OS). Mean follow-up period for patients that were diagnosed with advanced-stage
carcinoma was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3
and 21 months for short-term survivors, respectively. Intense mRNA signals were detected more frequently in tumor cells of
short-term survivors with use of all four probes. Comparable findings were observed in peritumoral stromal cells with ISH
for MMP-2, MMP-9 and TIMP-2 mRNA. Notably, primary tumors with intense mRNA signal for TIMP-2 (No = 14) were uniformly associated
with a fatal outcome. In univariate analysis of primary tumors, mRNA levels of TIMP-2 in stromal cells (P = 0.0002), as well as for MMP-9 (P = 0.012) and TIMP-2 (P = 0.02) in tumor cells, correlated with poor outcome. In univariate analysis of metastatic lesions, mRNA levels of TIMP-2
in stromal cells (P = 0.031), as well as for MMP-2 (P = 0.027) and MT1-MMP (P = 0.008) in tumor cells, correlated with poor outcome. Interestingly, the presence of MT1-MMP in stromal cells correlated
with longer survival (P = 0.025). In a multivariate analysis of ISH results for primary tumors, TIMP-2 levels in stromal cells (P = 0.006) and MMP-9 levels in tumor cells (P = 0.011) retained their predictive value. We conclude that MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid markers of poor survival
in advanced-stage ovarian carcinoma.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
9.
Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors 总被引:3,自引:0,他引:3
Gokaslan ZL Chintala SK York JE Boyapati V Jasti S Sawaya R Fuller G Wildrick DM Nicolson GL Rao JS 《Clinical & experimental metastasis》1998,16(8):721-728
Matrix metalloproteinases (MMPs) have been implicated in the process of tumor invasion and metastasis formation. Thus, we determined the expression of MMPs in various primary and metastatic spinal tumors in order to assess the role of these enzymes in spinal invasion. MMP expression was examined by immuno-histochemical localization, and quantitative evaluation of MMP protein content was determined by enzyme-linked immunosorbant assay (ELISA) and Western blotting. MMP enzyme activity was determined by gelatin zymography. Lung carcinomas and melanomas metastatic to the spine were shown to have higher levels of MMP-9 activity than those of breast, thyroid, renal metastases and primary spinal tumors. Immunohistochemical analysis revealed similar difference in expression of MMP-9 in tissue samples. When the tissue samples were subjected to gelatin zymography for examination of MMP-2 and MMP-9 activity and to ELISA and Western blotting for quantitative estimation of protein content, the most striking results were obtained for lung carcinomas and melanomas relative to the other tumors. Lung carcinomas and melanomas metastatic to the spine had considerably higher levels of MMP-9 activity than those of primary spinal tumor or breast, thyroid, and renal carcinoma metastases. Within the metastatic tumor category, neoplasms that are known to be associated with the shortest overall survival rates and most aggressive behavior, such as lung carcinomas and melanomas, had the highest levels of MMP-2 and MMP-9 activity compared to those less aggressive metastatic tumors such as breast, renal cell, and thyroid carcinomas. Our results suggest that MMPs may contribute to the metastases to the spinal column, and overexpression of these enzymes may correlate with enhanced invasive properties of both primary and metastatic spinal tumors.© Kluwer Academic Publishers 1998 相似文献
10.
Fleischmann A Rocha C Saxer-Sekulic N Zlobec I Sauter G Thalmann GN 《Virchows Archiv : an international journal of pathology》2011,458(6):741-748
Patients with nodal positive prostate cancers are an important cohort with poorly defined risk factors. CD10 is a cell surface
metallopeptidase that has been suggested to play a role in prostate cancer progression. CD10 expression was evaluated in 119
nodal positive prostate cancer patients using tissue microarrays constructed from primary tumors and lymph node metastases.
All patients underwent radical prostatectomy and standardized extended lymphadenectomy. They had no neoadjuvant therapy and
received deferred androgen deprivation. In the primary tumor, high CD10 expression was significantly associated with earlier
death from disease when compared with low CD10 expression (5-year survival 73.7% vs. 91.8%; p = 0.043). In the metastases, a high CD10 expression was significantly associated with larger total size of metastases (median
11.4 vs. 6.5 mm; p = 0.015), earlier death of disease (5-year survival 71.5% vs. 87.3%; p = 0.017), and death of any cause (5-year survival 70.0% vs. 87.2%; p = 0.001) when compared with low CD10 expression. CD10 expression in the metastases added independent prognostic information
for overall survival (p = 0.029) after adjustment for Gleason score of the primary tumor, nodal tumor burden, and resection margins. In conclusion,
a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in
the lymph node metastases and might help to personalize patient management. 相似文献
11.
Violetta Sulzyc-Bielicka Pawel Domagala Ewa Majdanik Maria Chosia Dariusz Bielicki Jozef Kladny Mariusz Kaczmarczyk Krzysztof Safranow Wenancjusz Domagala 《Virchows Archiv : an international journal of pathology》2009,454(6):695-702
Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical
characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major
target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect
of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal
to the splenic flexure. Nuclear TS was detected by immunohistochemistry with a TS 106 monoclonal antibody on tissue microarrays
constructed from 269 CRCs. The median histological score of nuclear TS expression of all proximal tumors was two times higher
(p = 0.0003) and in men three times higher (p = 0.00023) than that found in distal tumors. In multivariate analysis which included age, sex, Astler–Coller stage, histological
grade, and site, only proximal location of the tumor was identified as an independent factor associated with higher TS expression
(odds ratio 2.46, 95% confidence interval = 1.29–4.70, p = 0.0062). These results demonstrate significant differences in nuclear TS expression between proximal and distal cancers
and suggest the potential importance of the site of the tumor for proper stratification of patients for chemotherapy. 相似文献
12.
Anudep Rungsipipat Sirikajohn Tangkawatana Achariya Sailasuta Chainarong Lohachit Sunantha Chariyalertsak 《Comparative clinical pathology》2008,17(1):35-41
To evaluate the use of c-erbB-2 oncogene and p21
WAF1/CIP1
suppressor gene products as the prognosis markers for canine mammary tumors, expression of these gene products were examined
immunohistochemically using tumor tissues and clinical data from 96 dogs with malignant mammary tumors. Semiquantitative data
was compared with histopathological grades, proliferating cell nuclear antigen (PCNA)-positive index, and clinicopathological
matters. The expression c-erbB-2 protein was found in the cellular membrane and cytoplasm of neoplastic epithelial cells,
and the positive index had no significant relation to the histopathological features and PCNA-positive index, except for the
individual age of affected dogs (P < 0.05). The product of p21
WAF1/CIP1
was mostly found in cytoplasm and occasionally in the nucleus of neoplastic cells. The quantitative data had significant
association to the malignancy grade and size of tumors (P < 0.05). However, that had no significant relationship to the PCNA-positive index. The present study concluded that both
gene products could not apply as the direct markers to evaluate the prognosis of canine mammary tumors. The detection of c-erbB-2 product may be partly beneficial to the differential diagnosis of epithelial type of mammary cancer. The use of p21
WAF1/CIP1
product in prognosis of canine mammary cancer needs further investigation. 相似文献
13.
Sachiko Mori Ruby Pawankar Chika Ozu Manabu Nonaka Toshiaki Yagi Kimihiro Okubo 《Allergy, asthma & immunology research》2012,4(4):231-239
Purpose
Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells.Methods
Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays.Results
At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa.Conclusions
We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR. 相似文献14.
Sulzyc-Bielicka V Domagala P Urasinska E Bielicki D Safranow K Domagala W 《Virchows Archiv : an international journal of pathology》2011,458(4):431-438
In several, but not all, previous studies, positive p21WAF1 expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However,
it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21WAF1 expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler–Coller stage B2 and C patients
with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21WAF1 was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21WAF1 was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained
the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21WAF1 expression but not in the subgroup of 61 stage B2 patients with negative p21WAF1 expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21WAF1 expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21WAF1 in colorectal tumor cells identifies a subgroup of Astler–Coller stage B2 patients who could benefit significantly from 5FU-based
chemotherapy and may improve the selection of patients for adjuvant chemotherapy. 相似文献
15.
16.
Chih-Min Yang Yi-Zih Liu Jiunn-Wang Liao Miao-Lin Hu 《Clinical & experimental metastasis》2010,27(5):341-349
This study examined the anti-metastatic effects of oxythiamine (OT) both in cell culture and in vivo. Cell culture results
revealed that OT (0–20 μM) significantly inhibited the invasion and migration (IC50 = 8.75 μM) of Lewis lung carcinoma (LLC) cells. These effects of OT were accompanied by the inhibition of metalloproteinases-2
and -9 (MMP-2, MMP-9), urokinase-type plasminogen activator (uPA) activities and by the increases in protein expression of
tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1, TIMP-2). We then implanted (s.c.) C57BL/6 mice with LLC cells and
supplemented the mice with a low- or a high-dose of OT (250 or 500 mg/kg BW) daily for 5 wk. During the 5-wk period, OT supplementation
decreased plasma MMP-2 activity in a dose-dependent manner, and this effect was significant after 4 wk of tumor cell implantation.
Tumor metastasis was found to confine to the lungs of mice injected with the tumor cells. High-OT supplementation strongly
lowered the number and area of tumors and inhibited protein expression of MMP-2 and MMP-9 in the lungs. In addition, high-OT
supplementation markedly decreased the extent of proliferating cell nuclear antigen (PCNA) staining in the lungs. By contrast,
OT supplementation increased TIMP-1 and -2 protein expression in the lungs. These results demonstrate that OT supplementation
attenuates tumor cell metastasis, possibly via inhibition of protein expression of MMPs, extent of PCNA staining and via increase
of proteins expression of TIMPs. 相似文献
17.
Fabiano O. Poswar Carlos A.C. Fraga Lucyana C. Farias John D. Feltenberger Vitória P.D. Cruz Sérgio H.S. Santos Christine M. Silveira Alfredo M.B. de Paula André L.S. Guimarães 《Pathology, research and practice》2013
The expression of metalloproteinases and their inhibitors has been related to different invasive and metastatic potentials in cancer. This study aims to investigate the immunohistochemical expression of TIMP-3 and MMP-9 in samples of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC), and actinic keratosis (AK). Immunohistochemistry was performed to evaluate the expression of TIMP-3 and MMP-9 in samples of BCC (n = 22), SCC (n = 10), and AK (n = 15). Ten fields of both tumor parenchyma and tumor stroma were photographed and counted in image software. The ratio of positive cells to total cells was used to quantify the staining. A higher expression of MMP-9 was found in tumor stroma of SCC compared to BCC and AK. No significant differences in TIMP-3 expression were observed among the groups. Considering the well-described differences between these neoplasms, these results provide additional evidence of the role of MMP-9 in tumor invasiveness of keratinocyte-derived tumors. 相似文献
18.
Lerma E Romero M Gallardo A Pons C Muñoz J Fuentes J Lloveras B Catasus L Prat J 《Virchows Archiv : an international journal of pathology》2008,452(1):65-74
We studied whether Fas-receptor (Fas-R; CD95) expression, single-nucleotide polymorphisms (SNPs) in the Fas promoter region,
and/or Fas-ligand (Fas-L) production could determine individual susceptibility to cervical cancer progression. The clinicopathologic
features of 38 patients with cervical squamous carcinomas (22 stage I, 8 stage II, and 8 stage III+) were reviewed and related
with: (a) Fas-R expression by immunohistochemistry; (b) Fas-R SNPs at -670 and -1377 locations by restriction fragment length
polymorphism and DNA sequencing; and (c) Fas-L expression by immunohistochemistry. Overall and disease-free survival curves
showed significant differences in relation to stage (p < 0.001). Fas-R was identified in 20 of 38 (52.6%) tumors without statistical differences in survival, stage, or Fas-L overproduction.
Fas-R GG genotype was more common than expected in advanced tumors (p = 0.065). The Fas-R-1377A allele and AA genotype were unrelated with survival, stage, or Fas-R expression. Fas-L overproduction
was detected in 20 of 38 (52.6%) tumors; it was more frequent in advanced-stage tumors and was inversely related to survival
(p = 0.03) and decrease in host inflammatory response (p = 0.01). Fas-R expression by tumor cells seems unrelated to stage or lymphoid infiltrate. Tumor production of Fas-L may represent
an attempt to destroy the host’s lymphocytic reaction. 相似文献
19.
Immunolocalisation studies of matrix metalloproteinases-1, -2 and -3 in human melanoma 总被引:1,自引:0,他引:1
The matrix metalloproteinases (MMPs) are considered to have an important role in connective tissue degradation and have been
implicated in the mechanisms of tumour invasion and metastatic spread. We have used immunohistochemistry to examine and compare
the tissue distributions of collagenase-1 (MMP-1), gelatinase A (MMP-2) and stromelysin-1 (MMP-3) in 18 specimens of malignant
melanoma, viz. 10 superficial spreading and 8 nodular melanomas. MMPs-1, -2 and -3 were demonstrated within melanoma and host
tissue cells, especially at the periphery of some tumours, but were usually restricted to less than 10% of total melanoma
cells. The MMPs were absent from ’normal’ skin tissue distant from the tumour. MMP-2 was localised to discrete groups of cells
and was especially evident at the epidermal:tumour interface, whereas MMP-3 was mainly confined to the deeper margins of melanoma.
No regular pattern of MMP expression was observed for either the superficial spreading or the nodular melanomas. The variable
distributions of the MMPs suggested that enzyme expression was subject to local microenvironmental regulation, possibly in
response to matrix components and the cellular heterogeneity observed at the tumour margins. These in situ observations add
weight to the concept that specific MMPs contribute to the mechanisms of tumour invasion.
Received: 10 March 1999 / Accepted: 6 July 1999 相似文献