共查询到20条相似文献,搜索用时 15 毫秒
1.
Protease-activated receptor (PAR) 1, PAR3, and PAR4 are considered "thrombin receptors" because thrombin specifically cleaves the extracellular N-termini of the receptor to unmask a new amino acid terminus, which in turn acts as a peptide ligand by binding intramolecularly to the body of the receptor. Among those 3 family members, PAR1 is the predominant thrombin receptor. Although the thrombin-mediated regulation of clot formation has been studied extensively over the past decades, the possible role of thrombin in tumor metastasis via PAR1 has only recently received attention and is briefly discussed herein. 相似文献
2.
J Li A D Guillebon J-w Hsu S R Barthel C J Dimitroff Y-F Lee M R King 《British journal of cancer》2013,109(12):3014-3022
Background:
The interaction between human prostate cancer (PCa) cells and bone marrow (BM) endothelium follows a rolling-and-adhesion cascade mediated by E-selectin ligand (ESL): E-selectin. This adhesion is enabled by elevated expression of α-1,3-fucosyltransferases (FTs), enzymes responsible for ESL-mediated bone metastasis in humans. In contrast, the incidence of bone metastasis in mice is rare.Methods:
FT 3, 6 and 7 were overexpressed in mouse PCa cells. The rolling cell number, cell-rolling velocity and transendothelial migration were characterised in vitro. Fucosyltransferases-transduced mouse PCa cells expressing luciferase were inoculated into mice via left ventricle to compare the capability of bone metastasis. Mass spectrometry and immunoprecipitation were utilised for identification of ESLs.Results:
Overexpression of FT3, FT6 or FT7 restored ESLs and enabled mouse PCa cells to roll and adhere in E-selectin-functionalised microtubes, similar to trafficking of circulating PCa cells in BM vessels. Following intracardiac inoculation, FT6-transduced cells induced robust bone metastasis in mice. Inhibition of FT6 by a fucose mimetic significantly reduced bone metastasis. Importantly, comparison of FT3, FT6 and FT7 gene expression in existing clinical samples showed significant upregulation of FT6 in PCa-distant metastases.Conclusion:
FT6 is a key mediator of PCa cells trafficking to the BM. It may serve as a viable drug target in preclinical tests of therapeutics for reduction of PCa bone metastasis. 相似文献3.
Osteopontin: possible role in prostate cancer progression. 总被引:10,自引:0,他引:10
G N Thalmann R A Sikes R E Devoll J A Kiefer R Markwalder I Klima C M Farach-Carson U E Studer L W Chung 《Clinical cancer research》1999,5(8):2271-2277
Human prostate cancer has the propensity to metastasize to the bone where reciprocal cellular interactions between prostate cancer and bone cells are known to occur. Osteopontin (OPN), a noncollagenous bone extracellular matrix, is a secreted adhesive glycoprotein with a functional RGD cell-binding domain that interacts with the alpha(v)beta3 cell surface integrin heterodimer. OPN has been associated with malignant transformation as well as being ligand to the CD44 receptor. Polyclonal antibodies to human OPN (hOPN) were prepared, and specificity was shown by preabsorption with recombinant hOPN. The stimulatory effect of hOPN protein and the inhibitory effect of hOPN antibody on human prostate cancer cell lines LNCaP and C4-2 were assessed by induction or inhibition of anchorage-independent growth, respectively. Expression of hOPN mRNA in prostate cancer cell lines and human prostate cancer tissue specimens were measured by mRNA blot analysis. Protein expression was assessed by immunohistochemistry in human prostate cancer specimens and by Western blot analysis in prostate cancer cell lines. hOPN stimulated anchorage-independent growth of the human prostate cancer cell lines LNCaP and C4-2 in vitro. Antibodies to hOPN inhibited the growth-stimulatory effect by endogenous OPN, which can be overcome by the addition of exogenous hOPN. hOPN mRNA and protein are expressed in human prostate cancer cell lines in vitro and in clinical human prostate cancer specimens. These findings taken together suggest that OPN may act as a paracrine and autocrine mediator of prostate cancer growth and progression. 相似文献
4.
Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. 总被引:16,自引:0,他引:16
The mechanism underlying the "organ-specific" metastasis of prostate cancer cells to the bone is still poorly understood. It is not clear whether the cells only invade the bone and proliferate there or whether they invade many tissues but survive mainly in the bone ("seed and soil"). Extracts from various organs were used as chemoattractants in the in vitro chemotaxis and invasion assays. Results show that, in comparison with extracts of other tissues, bone extracts promote a 2- to 4-fold increase in chemotaxis by human prostate epithelial cells and a 4-fold increase in the invasive ability of human prostate carcinoma cells. The purified active factor from bone and from marrow stromal-cell-conditioned medium is a low glycosylated osteonectin that specifically promotes the invasive ability of bone-metastasizing prostate (and breast) cancer cells but not that of non-bone-metastasizing tumor cells. It does not stimulate the growth of prostate cancer cells in vitro or in vivo. Because osteonectin specifically enhances matrix metalloprotease activity in prostate and breast cancer cells (and not in other tumor cell types), we conclude that prostate cancer cell metastasis to the bone is, in part, mediated by the ability of osteonectin to promote migration, protease activity, and invasion. 相似文献
5.
Mo L Zhang J Shi J Xuan Q Yang X Qin M Lee C Klocker H Li QQ Mo Z 《Anticancer research》2010,30(9):3413-3420
Human tissue kallikrein 7 (hK7), a chymotrypsin-like secreted serine protease, catalyzes the degradation of intercellular adhesive structures in the cornified layer of the skin, leading to desquamation. Thus, hK7 is implicated in cancer invasion and metastasis. Although hK7 is highly expressed in prostate tissues, its biological role in prostate cancer progression is poorly understood. In the current study, we established an hK7-expressing cell model for prostate tumors by stably transfecting prostate carcinoma 22RV1 and DU145 cells with an expression vector encoding hK7. We found that there were no obvious differences in cell proliferation between cells overexpressing hK7 and cells transfected with empty vector (p>0.05). Intriguingly, a Matrigel invasion assay revealed that hK7 remarkably increased the migration and invasion of prostate cancer cells (p<0.01). Furthermore, hK7 induced epithelial-mesenchymal transition-like changes in prostate carcinoma cells, as evidenced by scattered cellular growth, mesenchyma-like morphology, and up-regulated expression of vimentin, a mesenchymal marker. These novel findings suggest that hK7 plays an important role in mediating prostate cancer progression and that hK7 promotes invasion and metastasis, at least in part, through inducing the epithelial-mesenchymal transition of prostatic carcinoma cells. 相似文献
6.
Human mesenchymal stem cells (hMSCs) play an important role in the development of human cancers. In the present study, we observed that hMSCs promoted human prostate cancer (PCa) cell PC-3 growth in vivo and in vitro. The conditional medium of hMSCs promoted the proliferation, migration, and invasion of PC-3 cells. The expression of MMP-2 and MMP-9 in PC-3 was upregulated by conditional medium of hMSCs. In addition, blocking tumor transformation factor beta (TGFβ) blunted the pro-oncogenic function of hMSCs. These results suggest that hMSCs may play a pro-oncogenic role in the growth of human prostate caner by producing TGFβ. 相似文献
7.
Bronzetti E Artico M Forte F Pagliarella G Felici LM D'Ambrosio A Vespasiani G Bronzetti B 《Oncology reports》2008,19(4):969-974
Many studies have demonstrated that both normal and malignant prostate cells respond to a variety of growth factors, while several significant differences were found between normal and tumoural cells. The aim of this study was to focus on the localization and distribution of the immuno-reactivity for neurotrophins (NTs) and neurotrophin receptors (NTRs) in normal, hyperplastic and prostate cancer cells, obtained from 40 subjects. We studied samples obtained from 16 prostate cancer (PC, retropubic radical prostatectomy), 20 benign prostatic hyperplasia (BPH, supra-pubic prostatectomy) and normal peripheral prostate tissue from four fresh male cadavers. Samples were examined via immunohistochemical techniques in order to detect the expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and their own receptors TrkA, p75, TrkB and TrkC. We observed a high expression of BDNF and TrkB in PC and BPH, though no immuno-reactivity was found for p75. Low expression was reported by other NTs and NTRs in the normal peripheral prostate zone, BPH and PC. These data suggest a possible predictive role for NTs and NTRs, especially for BDNF and TrkB, in the diagnosis and/or management of prostate cancer. The absence of p75 expression confirms its supposed role in apoptotic phenomenon. 相似文献
8.
9.
Metastasis to bone is common in lung, kidney, breast and prostate cancers. However, prostate cancer is unique in that bone is often the only clinically detectable site of metastasis, and the resulting tumours tend to be osteoblastic (bone forming) rather than osteolytic (bone lysing). The interaction between host cells and metastatic cancer cells is an important component of organ-specific cancer progression. How can this knowledge lead to the development of more effective therapies? 相似文献
10.
Ubiquitin C-terminal hydrolse-L1 (UCH-L1) is a deubiquitinating enzyme (DUB) that cleaves the ubiquitin (ub) moiety from ub precursors or protein substrates. The correlation between UCH-L1 and cancer has been reported in various tissues, but the role of UCH-L1 in prostate cancer has not been thoroughly researched. Here we found that UCH-L1 is specifically highly expressed in the metastatic DU145 prostate cancer cell line, but not in the benign or weakly metastatic prostate cancer cells. To determine the role of UCH-L1 in prostate cancer metastasis, we constructed UCH-L1-knockdown DU145 and UCH-L1 or the active site mutant form of UCH-L1 (UCH-L1 C90S) expressing RWPE1 stable cells. Notably, the expression of UCH-L1 in RWPE1 cells promotes epithelial-to-mesenchymal transition (EMT), and this is an important process for cancer cell invasion and metastasis. On the contrary, knockdown of UCH-L1 in DU145 cells induces MET, the reverse program of EMT. Furthermore, the change of EMT status caused by altering the UCH-L1 level affects the migration and invasiveness of prostate cancer cells. Our results indicate that UCH-L1 promotes prostate cancer metastasis through EMT induction and UCH-L1 could be a novel diagnostic and therapeutic target for prostate cancer treatment. 相似文献
11.
Prostate cancer (PCa) is the most common malignancy in men. Although mortality from PCa has been declining over the past decade,
metastasis can substantially shorten survival time and remains a major challenge in maintaining quality of life for survivors.
PCa cells preferentially metastasize to bone and typically result in osteoblastic lesions. In the late stages of disease,
however, osteolytic lesions are observed. The mechanisms of PCa bone metastasis are still unclear, but relationships between
the PCa cells and the bone tissue elements are suspected of being more complex than initially thought. Far from being an innocent
bystander, the bone participates actively in the metastatic process and provides the cancer cells with growth factors and
a fertile environment. Among the various cells in the bone environment, osteoblasts have a central role through their bidirectional
interactions with the PCa cells. This review discusses the possible mechanisms of PCa bone metastasis and highlights the essential
role of osteoblasts in the metastasis of PCa to bone. 相似文献
12.
Fosså SD Lilleby W Waehre H Berner A Torlakovic G Paus E Olsen DR 《International journal of radiation oncology, biology, physics》2003,57(1):33-41
PURPOSE: To evaluate the postradiotherapy 5-year cancer-specific (CSS), clinical progression-free (cPFS), and overall (OS) survival rates in patients with pN0 M0 prostate cancer (PC). METHODS: Between 1989 and 1996, 203 consecutive pN0 M0 PC patients (T1-2, 66; T3-4, 137) received conformal prostatic four-field radiotherapy (median target dose 66 Gy). Any hormone manipulation was delayed until clinical progression (growth of the primary tumor or development of distant metastases). RESULTS: After a median observation time of 87 months (range 11-156), 99 patients had relapsed clinically and 70 patients were dead, 37 of them as a result of prostate cancer. Five-year CSS, cPFS, and OS rates were, respectively, 90% (95% CI 86-94%), 64% (95% CI 57-71%), and 82% (95% CI 77-87%), with no difference of OS compared with age-matched males from the general population. Gleason score (< or =7A vs. > or =7B) and the T category predicted cPFS, whereas CSS was associated with Gleason score only. Preradiotherapy PSA failed to predict survival. Patients with T1-2 Gleason score < or =7A had a 97% 5-year CCS, as compared with 89% for all other patients. A median of eight lymph nodes (range 0-29) were described in the specimens from pelvic lymphadenectomy (LA). CONCLUSION: Despite still preliminary observations, our 5-year results challenge the use of combined hormone radiotherapy in patients who are proven to be pN0 by preradiotherapy LA; in particular, in patients with T1-2/Gleason score < or =7A, whereas the survival in all other patients with pN0 M0 prostate cancer may be improved by adjuvant androgen deprivation. 相似文献
13.
Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis 总被引:4,自引:0,他引:4
Schmitz M Grignard G Margue C Dippel W Capesius C Mossong J Nathan M Giacchi S Scheiden R Kieffer N 《International journal of cancer. Journal international du cancer》2007,120(6):1284-1292
The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis. 相似文献
14.
15.
Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells. 总被引:5,自引:0,他引:5
Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host-tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through the sequential inoculation of bone marrow-derived carcinoma cells into the left ventricle and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells was significantly higher than the adhesion to other bone-derived cells, including nonendothelial bone marrow stromal cells (3.5x) and osteoblasts (1.7x). It was also significantly higher than the adhesion to rat fibroblasts (7x) and to hepatic endothelial cells (7.5x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone. 相似文献
16.
Metastasis in breast cancer significantly increases morbidity and mortality. The 5-year survival rate reduces from 90% for localised disease to about 20% once metastasis has taken place. The phosphoinositide 3-kinase/Akt signalling pathway has an important role in cell motility, invasion and metastasis. However, the precise contribution of the Akt kinase family members, Akt1, Akt2 and Akt3, in mediating these processes is unclear. The possibility that they have distinct functions in tumour progression is particularly interesting. 相似文献
17.
Metastasis in breast cancer significantly increases morbidity and mortality. The 5-year survival rate reduces from 90% for localised disease to about 20% once metastasis has taken place. The phosphoinositide 3-kinase/Akt signalling pathway has an important role in cell motility, invasion and metastasis. However, the precise contribution of the Akt kinase family members, Akt1, Akt2 and Akt3, in mediating these processes is unclear. The possibility that they have distinct functions in tumour progression is particularly interesting. 相似文献
18.
Solid tumours need to induce their own vascular supply, and microvessel density (MVD) has emerged as a prognostic factor in several tumours. We hypothesized that mRNA levels of some endothelial factors in prostate cancer tissue would correlate with histologically measured MVD, or other pathological parameters. Expression levels of the endothelial factors CD31, CD34, CD105, CD144, CD146, CAV1 and VEGFR2 were assessed by RT-qPCR in matched freshly frozen normal and tumour tissues from 69 patients that underwent radical prostatectomy. The results were compared to pathological parameters and the MVD in the corresponding paraffin-embedded material, as determined by immunohistochemistry against CD31 and CD34. Comparing mRNA expression in matched normal and tumour samples, only CAV1 showed relevant differences, being down-regulated in tumour tissues (fold change=-1.89, P<0.0001). CAV1 down-regulation correlated with pT category (P=0.006) and the Gleason score (P=0.041). In a univariate analysis, lower CAV1 mRNA expression was associated with biochemical recurrence (P=0.019). By immunohistochemistry, CAV1 was mainly localized in endothelial and stromal cells and showed a weaker staining pattern in the tumour compared to normal tissue. Furthermore, MVD significantly correlated with tumour grade and pT category. There was no significant association between endothelial mRNA expression and histologically determined MVD in tumour tissues, but only a trend for CD31 mRNA (P=0.074) and an inverse trend for CAV1 mRNA (P=0.056). In conclusion, there is only a weak correlation between the mRNA expression of endothelial factors and MVD in prostatic tumour tissue. However, loss of CAV1 mRNA expression may play a role in prostate cancer progression. 相似文献
19.