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1.
Long Jin MD Elzbieta Kulig PhD Xiang Qian MD Bernd W. Scheithauer MD Norman L. Eberhardt PhD Ricardo V. Lloyd MD PhD 《Endocrine pathology》1998,9(2):169-184
Human pituitary cells proliferate very slowly in vitro. Only a few cell lines have been established, and these have been used
mainly for short-term studies. To obtain immortalized cell lines of human pituitary adenomas for in vitro studies, we infected
adenoma cells with a replication-defective recombinant human adenovirus, which contains an SV40 early large T-antigen. One
of the cell lines (HP75), which has been studied in culture during 60 passages, has been extensively characterized. It expressed
the large T-antigen protein and its mRNA, as well as the genes for FSH-β, LH-β and α-subunit (α-SU) of gonadotropin hormone.
The HP75 cell line also expressed the genes of various members of the chromogranin (Cg)/secretogranin (Sg) family, including
CgA as well as the prohormone convertases PC1/3 and PC2. CgA was processed to pancreastatin in vitro, which was secreted into
the culture medium. Treatment with phorbol 12-myristate 13-acetate (PMA), TGF-β1, and forskolin increased CgA expression in
the cells and stimulated pancreastatin secretion into the medium while inhibiting cell growth. The HP75 cell line also expressed
TGF-β mRNA isoforms (β1, β2, β3) and the mRNAs for the receptors for TGF-β (RI, RII, and RIII). The cells responded to TGF-β1
in vitro by increasing CgA protein expression and pancreastatin secretion. TGF-β-RII protein and mRNA expression were both
increased by PMA.
Ultrastructural studies showed that the HP75 cells had very few dense-core secretory granules and a poorly developed Golgi
complex. After treatment with TGF-β1 and PMA, there was an increase in the development of rough endoplasmic reticulum and
the Golgi complex.
This is the first report of the development of an immortalized human pituitary cell line that retains some differentiated
functions. HP75 can be used to study TGF-β and CgA functions in pituitary cells. Replication-defective recombinant human adenovirus
with an SV40 large T-antigen insert can be used to generate other immortalized human pituitary cell lines for in vitro studies. 相似文献
2.
Dörner A Grunert HP Lindig V Chandrasekharan K Fechner H Knowlton KU Isik A Pauschinger M Zeichhardt H Schultheiss HP 《Journal of molecular medicine (Berlin, Germany)》2006,84(10):842-851
Coxsackie adenovirus receptor (CAR) is involved in immunological processes, and its soluble isoforms have antiviral effects on coxsackievirus B3 (CVB3) infection in vitro. We explored in this study the impact of CAR4/7, a soluble CAR isoform, on CVB3-induced myocarditis in BALB/c mice. BALB/c mice were treated daily with recombinant CAR4/7, β-galactosidase (β-Gal; as control protein) or buffer for 9 days. Half of each group was infected with CVB3 on day 3, and all mice were killed on day 9. Myocardial CVB3 titer, histology, and serology were analyzed. Treatment with CAR4/7 led to a significant reduction of myocardial CVB3 titer, whereas the application of β-Gal had no detectable effect on the myocardial virus load. CAR4/7 application, however, resulted in increased myocardial inflammation and tissue damage in CVB3-infected hearts, whereas β-Gal caused a degree of cardiac inflammation and injury similar to that in buffer-treated CVB3-infected control animals. CAR4/7 and β-Gal treatment induced the production of antibodies against the respective antigens. CAR4/7-, but not β-Gal-specific, virus-negative sera reacted against myocardial tissue and cellular membranous CAR, and significantly inhibited CVB3 infection in vitro. Thus, CAR4/7 suppressed CVB3 infection in vivo, supporting the concept of receptor analog in antiviral therapy. However, CAR4/7 treatment also leads to an aggravation of myocardial inflammation and injury most likely secondary to an autoimmune process. 相似文献
3.
Expression profiling and interferon-beta regulation of liver metastases in colorectal cancer cells 总被引:6,自引:0,他引:6
Liver metastasis is the major cause of death among colorectal cancer patients. Many gene products have been associated with
the colon cancer cells' ability to metastasize to the liver, including carcinoembryonic antigen (CEA) and mucins. In this
study we examined changes in expression of 384 genes in a model of human colorectal cancer metastasis in nude mice. Using
DNA microarrays, we compared expression between MIP-101 cells, a poorly metastatic human colon cancer cell line, with an interferon-beta
(IFN-β) resistant subline of MIP-101 (β-MIP) that is metastatic to the liver. Treatment of β-MIP cells with increasing concentrations
of IFN-β caused a reversion to the non-metastatic phenotype. The array data showed down-regulation of genes involved in apoptosis
in β-MIP cells and their return to the MIP-101 pattern upon IFN-β treatment. Cluster analysis also showed involvement of genes
belonging to cell cycle, angiogenesis and invasion pathways. Selected genes were chosen to validate the microarray data by
semi-quantitative RT-PCR. Association between gene expression pattern and metastatic phenotype was verified by intra-splenic
injection in nude mice. The number of genes examined in this study was small, but carefully selected. Significant changes
associated with cell growth and survival were observed, which gave the metastatic cells an advantage to grow in the liver.
This information may help identifying new markers for colorectal cancer prognosis as well as aid the development of new therapeutic
approaches.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
4.
5.
Shamekh R Cameron DF Willing AE Saporta S 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2006,170(2):277-284
Neural transplantation is developing as a successful treatment for neurodegenerative diseases such as Parkinson’s disease.
The human Ntera-2/D1 (NT2) cell line is an attractive alternative to the use of human fetal neurons as a cell source for transplantation.
We have explored combining NT2 cells, as a neuronal source, and Sertoli cells, which may act as a graft facilitator to enhance
neuronal survival and differentiation, and ameliorate the host immune response, into a tissue construct for use in cell replacement
therapy for neurodegenerative disease. This Sertoli-NT2-aggregated cell (SNAC) tissue construct is formed in the high aspect
ratio vessel (HARV) bioreactor. NT2 cells differentiate to dopaminergic NT2N neurons within the SNAC tissue construct without
retinoic acid. We report here that the gap junction protein connexin 43 is decreased among differentiated NT2N neurons. Inhibition
of connexin 43 with 18β glycyrrhetinic acid and carbenoxolone, a glycyrrhetinic acid derivative, during formation of the SNAC
tissue constructs disrupts the differentiation of NT2 cells. Therefore, connexin 43 is important in the differentiation of
NT2 cells in the SNAC tissue construct. 相似文献
6.
Seike T Fujita K Yamakawa Y Kido MA Takiguchi S Teramoto N Iguchi H Noda M 《Clinical & experimental metastasis》2011,28(1):13-25
The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived
brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental
model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks
of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were
observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around
metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured
mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were
activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen
activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1
β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression
of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells
but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other
lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each
other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain. 相似文献
7.
Yamamoto N Yang M Jiang P Tsuchiya H Tomita K Moossa AR Hoffman RM 《Clinical & experimental metastasis》2003,20(2):181-185
Metastasis to the lung is often a lethal event in sarcoma as well as other cancers. We report here a new animal model of sarcoma
enabling the external real-time fluorescence imaging of spontaneous lung metastasis. The human fibrosarcoma cell line HT-1080
was transduced with the green fluorescent protein (GFP) gene. HT-1080-GFP cells were injected into the right hind footpad
of severe combined immunodeficient (SCID) mice. The lung metastases were evaluated by whole-body fluorescence imaging as well
as direct-view imaging in live animals through a skin-flap window over the chest wall. Spontaneous lung metastases were observed
on the lungs of 11 of 12 mice. SCID mice well tolerated the skin-flap procedure enabling real-time imaging of spontaneous
lung metastases with a resolution of approximately 50–100 μm. This procedure enabled external imaging at the micrometastasis
level. Real-time evaluation of spontaneous lung metastasis in the same animals should allow drug evaluation and mechanistic
studies not previously possible.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
8.
Pelosi G Scarpa A Veronesi G Spaggiari L Del Curto B Moore PS Maisonneuve P Sonzogni A Masullo M Viale G 《Virchows Archiv : an international journal of pathology》2005,447(6):969-977
Nuclear translocation of β-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation
in nonsmall cell lung cancer. Less is known on β-catenin transactivation in high-grade pulmonary neuroendocrine tumors and
on the status of β-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or β-catenin target genes
cyclin D1 and matrix metalloproteinase-7 (MMP-7). β-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine
carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for β-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. β-catenin was
expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed
immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining
along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated
with EGFR and HER-2 protein expression. β-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and
two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These
cases, however, did not show β-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear β-catenin and
any clinicopathological variable including patients' survival. The subcellular compartmentalization of β-catenin is profoundly
altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows β-catenin nuclear accumulation
in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification
or expression.
The authors have no significant financial or other relationship with the manufacturers of any commercial products or commercial
services presented in this paper 相似文献
9.
Unexpected Immunoresponse to Gal and APA Antigens in Diabetic Type 1 Patients Receiving Neonatal Pig Islets After 6 Years 总被引:1,自引:0,他引:1
Valdés-González RA Dorantes LM Garibay GN Bracho-Blanchet E Dávila-Pérez R Terán L Ormsby CE Ayala-Sumuano JT Copeman L White DJ 《Journal of clinical immunology》2007,27(3):266-274
Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in
type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and
porcine nature of the surviving cells and the immune responses elicited toward Gal α(1,3)-Gal β(1,4)-GlcNAc (Gal) antigen
in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain
insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally,
all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response
to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels
promptly returned to basal values after 3–4 months. The long-term survival of porcine cells and the reduced humoral immune
response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating
that it is probably an immune accommodation of the graft. 相似文献
10.
Ebenezer Chitra Shu-Ling Yu Kuang-Nan Hsiao Charles Sia Shih-Yang Hsieh Yen-Hung Chow 《Virology》2009,393(1):120-126
Jaagsiekte sheep retrovirus (JSRV) that causes contagious ovine pulmonary adenocarcinoma (OPA) in sheep carries an oncogenic Envelope gene (Env), which is capable of transforming target cells in vitro and in vivo. We cloned full-length JSRV Env cDNA into an expression vector, SPC/SV40, where the transgene was driven by lung-specific surfactant protein C (SPC) promoter, to obtain SPC-JSRV Env construct. SPC-JSRV Env was microinjected into immunocompetent FVB/N mice embryos to generate Env transgenic mice. We obtained two lines of transgenic mice, both of which were capable of developing spontaneous lung tumors from 1 month onwards and the tumor incidence rate was about 56% at the age of 7 months in Env Transgenic line 1 and about 71% at the age of 6 months in Env Transgenic line 2. We were able to correlate higher tumor incidence rate and tumorigenicity in Env Transgenic line 2 to higher level of expression of Env transgene compared to Env Transgenic line 1. Immunohistochemical analysis showed that the tumor was primarily composed of type II pneumocytes where SPC promoter is known to be active similar to natural infection of JSRV in sheep. Analysis of cellular mitogenic signal transduction pathways revealed significant induction of p44/42 ERK pathway in the transgenic mice lungs with tumors compared to the lungs from non-transgenic FVB/N mice. Tumors in our transgenic mice pose similarities to human lung adenocarcinoma and therefore our mice could serve as a model system for evaluating the mechanisms of lung tumorigenesis in vivo. 相似文献
11.
Ramos OH Kauskot A Cominetti MR Bechyne I Salla Pontes CL Chareyre F Manent J Vassy R Giovannini M Legrand C Selistre-de-Araujo HS Crépin M Bonnefoy A 《Clinical & experimental metastasis》2008,25(1):53-64
The integrin αvβ3 is involved in multiple aspects of malignant cancer, including tumor angiogenesis and metastasis, which makes the receptor
a key target for the development of anti-cancer therapies. We report here on the production, the characterization and the
in vivo anti-angiogenic and anti-metastatic properties of a novel αvβ3-binding disintegrin, DisBa-01, isolated from a cDNA library made with RNAs from the venom gland of Bothrops alternatus. The 11,637 Da-recombinant monomeric form of DisBa-01 displayed an RGD motif and interacted with purified αvβ3 integrin in surface plasmon resonance studies, in a dose-dependent and cation sensitive manner. A three-dimensional molecular
model of DisBa-01 in complex with αvβ3 predicted a large surface of contacts with the β3 subunit. DisBa-01 inhibited the adhesion of αvβ3-expressing human microvascular endothelial cell line-1 (HMEC-1) and murine melanoma cell line B16F10 to vitronectin (IC50 = 555 nM and 225 nM, respectively), and transiently inhibited their proliferation without direct cell toxicity, but did not
affect the binding nor the proliferation of a human breast cancer-derived cell line (MDA-MB-231) not expressing αvβ3. In vivo, DisBa-01 dose-dependently decreased bFGF-induced angiogenesis in a matrigel plug assay in athymic nude mice (IC50 = 83 nM). When injected intravenously to C57BL/6 mice together with B16F10 melanoma cells, DisBa-01 time- and dose-dependently inhibited lung metastasis monitored by bioluminescent imaging. We conclude that DisBa-01 is a potent new inhibitor of αvβ3-dependent adherence mechanisms involved in neo-vascularization and tumor metastasis processes.
Oscar H. P. Ramos and Alexandre Kauskot contributed equally to this work. 相似文献
12.
S. Frede C. Deetjen W. Schobersberger G. Hoffmann 《Pflügers Archiv : European journal of physiology》1998,436(2):233-237
The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor
α (TNFα) which itself is produced by a variety of tumour cells. We have recently reported that the human hepatoma cell line
HepG2 expresses the TNFα gene and releases biologically active TNFα protein after stimulation with interleukin-1β (IL-1β).
Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary for the proliferation and differentiation of neutrophil
progenitor cells in the bone marrow. In addition G-CSF has been reported to exert anti-inflammatory effects. In our study
we tested the effect of recombinant human G-CSF (rhG-CSF) on TNFα production in HepG2 cells. It could be shown that rhG-CSF
(250 U/ml) significantly reduced IL-1β-induced (300 pg/ml) TNFα gene expression after 1-h and 3-h incubation periods (TNFα
mRNA concentrations were: 8.8±2.1 amol/μg total RNA after a 1-h incubation with IL-1β versus 3.8±1.3 amol/μg total RNA after
a 1-h incubation with IL-1β + rhG-CSF and 13.8±2.2 amol/μg total RNA after a 3-h incubation with IL-1β versus 8.8±2.1 amol/μg
total RNA after a 3-h incubation with IL-1β + rhG-CSF). From these data we conclude that rhG-CSF is a potent inhibitor of
cytokine-induced TNFα production by tumour cells. Therefore, treatment of patients with malignant diseases with rhG-CSF might
represent a useful tool to improve the tumour-associated cachexia.
Received: 19 November 1997 / Received after revision and accepted: 9 February 1998 相似文献
13.
目的 克隆人B-CAM/Lu基因,构建其逆转录病毒表达载体,获得稳定高表达B-CAM/Lu的L929细胞株.方法 RT-PCR技术克隆人B-CAM/Lu基因,并插入逆转录病毒载体pEGZ中,该重组逆转录病毒载体与pH456、pH460两个辅助病毒载体一起,共转染包装细胞293T,并感染L929细胞,经Zeocin筛选获得的细胞株通过RT-PCR、Western blot及间接免疫荧光鉴定细胞中B-CAM/Lu基因mRNA的转录和蛋白表达.结果 成功获得人B-CAM/Lu基因,测序正确,亚克隆至逆转录病毒载体pEGZ后,经转染筛选,获得的抗性L929细胞株通过RT-PCR和Western blot分析,检测到B-CAM/Lu mRNA的转录和目的 蛋白的表达,通过间接免疫荧光确定该蛋白定位表达在L929转基因细胞膜上.结论 成功克隆并构建了人B-CAM/Lu基因的重组逆转录病毒表达载体,获得稳定高表达B-CAM/Lu蛋白的L929细胞株,为将其作为免疫源,制备B-CAM/Lu单抗用于镰刀型红细胞病及一些肿瘤疾病的检测诊断打下了基础. 相似文献
14.
Osteopontin regulates multiple functions contributing to human colon cancer development and progression 总被引:21,自引:0,他引:21
Osteopontin (OPN) is a secreted phosphoglycoprotein known to interact with a number of integrin receptors. While increased
OPN expression has been reported in a number of human cancers, and its cognate receptors (αv-β3, αv-β5, and αv-β1 integrins
and CD44) have been identified, its role in colon cancer development and progression has not been extensively studied. We
previously identified, using a combination of gene expression and tissue microarrays, that increased OPN expression is concordant
with tumor stage. The current study examined the functional role of OPN in colon cancer progression and metastatic potential.
The principal findings of this study were that both endogenous OPN expression (via stable transfection) as well as exogenous
OPN (added to culture medium) enhanced the motility and invasive capacity of human colon cancer cells in vitro. OPN appeared
to regulate motility though interaction with CD44. OPN expression also reduced intercellular (homotypic) adhesion, an important
characteristic of metastatic cancer cells. Stable transfection of four poorly tumorigenic human colon cancer cell lines with
OPN also resulted in enhanced tumorigenicity in vivo with increased proliferation and increased CD31 positive microvessel
counts, concordant with the degree of OPN expression. Collectively, these results suggest that OPN may affect multiple functional
components contributing to human colon cancer progression and solidifies its role in this process.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
15.
Specific cytotoxic T lymphocytes in gene therapy 总被引:1,自引:0,他引:1
U. Altenschmidt Dirk Moritz B. Groner 《Journal of molecular medicine (Berlin, Germany)》1997,75(4):259-266
Cytotoxic T lymphocytes possess the capacity to lyse target cells which express antigens on their surface recognized by the
T cell receptor. These cells are crucial in the body’s defense against foreign antigens. It has long been a goal of tumor
biology to utilize T cells, specialized in the elimination of unwanted cells, for the treatment of cancer. The killing activity
of T lymphocytes is restricted to specific antigen-presenting cells. For this reason the use of cytotoxic T cells in the elimination
of cancer cells is limited to cancer cells which present neoantigens on their surface. To circumvent this limitation we describe
a procedure in which the ζ component of the T cell receptor is genetically manipulated and equipped with an extracellular
recognition domain. Introduction of a chimeric gene, consisting of the ζ chain of the T cell receptor and a single-chain antibody
domain, into cytotoxic T lymphocytes results in T cells with a predetermined recognition specificity for particular tumor
cells. The MHC restriction of target cell recognition can be avoided and tumor cells recognized by the single chain antibody
domain can be recognized and lysed. Retroviral-mediated gene transduction was used to introduce chimeric ζ chain constructs
into primary T cells of mice. The cocultivation of retrovirus producing helper cells with in vitro activated T lymphocytes
led to a high gene transduction efficiency into primary T cells. These primary T cells assumed a predetermined specificity
for target cell recognition and lysis. The production and provision of tumor cell specific T lymphocytes might not be sufficient
to eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that transplanted tumors secrete transforming growth
factor β and thereby stifle the action of lymphocytes. We suggest that a coordinated strategy including the suppression of
tumor cells specific antilymphocyte action and the provision of tumor cell specific T cells might be required to successfully
eliminate tumor cells in vivo.
Received: 13 September 1996 / Accepted: 30 October 1996 相似文献
16.
目的:构建稳定表达人CXCR4基因的L929细胞株,分析CXCR4分子对转基因细胞迁移能力的影响。方法:TRIzol一步法抽提人外周血单个核细胞(PBMC)总RNA,RTPCR扩增出CXCR4基因,双酶切装入逆转录病毒载体pEGZTerm,与辅助病毒载体用脂质体法共转染包装细胞293T,用其培养上清感染L929细胞72h后,经Zeocin筛选出稳定表达CXCR4分子的L929细胞株;利用微孔隔离小室检测转人CXCR4基因的L929细胞在SDF-1α作用下的迁移能力。结果:构建含CXCR4基因的重组逆转录病毒载体,经转染包装细胞293T后,筛选获得能稳定高表达人CXCR4蛋白的L929转基因细胞,转入人CXCR4基因的L929细胞在SDF-1α作用下介导迁移。结论:成功构建转染人CXCR4细胞株,为肿瘤迁移模型的研究和鼠抗人CXCR4 mAb的制备打下基础。 相似文献
17.
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
18.
Some studies indicate that pituitary adenoma tissues are hypovascular and have lower oxygen saturation relative to the normal
pituitary gland and suggest that this may induce hypoxia. Our previous study showed that laminin β2 mRNA is upregulated under
hypoxic conditions (1% oxygen) but not under normoxic conditions (21% oxygen) in the HP-75 cell line. In the present study,
we further investigated the expression of laminin β1, 2, or 3 chain,under hypoxic and normoxic conditions in HP-75 cells using
Western blotting. We found that only laminin β2 had a significantly higher expression under hypoxia than under normoxia in
the HP-75 cell line. The expression of laminin β chains was investigated by fluorescent immunohistochemistry of paraffin-embedded
sections of tissue from pituitary adenomas of 42 cases (30 cases without apoplexy and 12 with apoplexy) categorized according
to Knosp grading and tumor size. We found that only laminin β2 expression correlated significantly with tumor size, but did
not correlate with apoplexy and invasiveness. In conclusion, laminin β2 can be regarded as a surrogate marker of hypoxia-as
its level is significantly elevated under hypoxic conditions, and it is predominantly expressed in pituitary macroadenomas. 相似文献
19.