Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma

Lang, Shona; Hyde, Catherine; Reid, Ian N.; Hitchcock, Ian S.; Hart, Claire A.; Bryden, A A G; Villette, Jean‐Marie; Stower, Michael J.; Maitland, Norman J.

doi:10.1002/pros.10088

Cited by 151 publications

(117 citation statements)

References 30 publications

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“…Vimentin is a characteristic marker for the mesenchymal phenotype of cancer cells, and enhanced vimentin expression was previously found in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma. 41 In line with these observations, we found that vimentin expression increased with tumorigenicity and that E-cadherin/vimentin ratios decreased with augmented invasiveness and aggressiveness (Figure 2a). BMP7 mRNA levels in prostate cancer cell lines strongly correlated to E-cadherin/vimentin ratio (Figure 2, a and b), whereas no association was observed for other BMPs (results not shown).…”

Section: Bmp7 Mrna Expression In Prostate Cancer Cell Linessupporting

confidence: 84%

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Buijs

Rentsch

Horst

et al. 2007

The American Journal of Pathology

181

160

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Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity. Because epithelial-to-mesenchymal transition is involved in cancer, we investigated whether BMP7 plays a role in prostate cancer growth and metastasis. BMP7 expression in laser-microdissected primary human prostate cancer tissue was strongly down-regulated compared with normal prostate luminal epithelium. Furthermore, BMP7 expression in prostate cancer cell lines was inversely related to tumorigenic and metastatic potential in vivo and significantly correlated to E-cadherin/vimentin ratios. Exogenous addition of BMP7 to human prostate cancer cells dose-dependently inhibited transforming growth factor ␤-induced activation of nuclear Smad3/4 complexes via ALK5 and induced E-cadherin expression. Moreover, BMP7-induced activation of nuclear Smad1/4/5 signaling transduced via BMP type I receptors was synergistically stimulated in the presence of transforming growth factor ␤, a growth factor that is enriched in the bone microenvironment. Daily BMP7 administration to nude mice inhibited the growth of cancer cells in bone. In contrast, no significant growth inhibitory effect of BMP7 was observed in intraprostatic xenografts. Collectively, our observations suggest that BMP7 controls and preserves the epithelial phenotype

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Section: Bmp7 Mrna Expression In Prostate Cancer Cell Linessupporting

confidence: 84%

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Buijs

Rentsch

Horst

et al. 2007

The American Journal of Pathology

181

160

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“…Importantly, the retargeted virus demonstrated no transduction above that of pc-Adluc, in the cells derived from normal prostate epithelia suggesting that the risk of inappropriate transgene expression in healthy tissue would be low. Although we detected b1 integrin subunits on both PNT1a and PNT2 cells in agreement with previous studies, 50,51 we would expect these cells to maintain b4 integrin subunit expression to which the a6 subunit would preferentially dimerize, SIKVAV being unable to bind integrin a6b4. 52 Summary of flow cytometric analysis using specific monoclonal anti-a6-integrin subunit and monoclonal anti-b1-integrin subunit antibodies on a panel of human cell lines.…”

Section: Discussionsupporting

confidence: 92%

Incorporation of a laminin-derived peptide (SIKVAV) on polymer-modified adenovirus permits tumor-specific targeting via α6-integrins

Stevenson

Hale

et al. 2007

Cancer Gene Ther

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Effective gene therapy for disseminated metastatic cancer is currently impossible because of poor delivery of vector to target sites. Modification of viral vectors to target advanced cancer has long been a challenge. In this study, we aimed to redirect adenovirus tropism to infect prostate cancer cells via a6b1 integrins, whose expression is upregulated during prostate cancer progression. To ablate normal mechanisms of infection and provide a framework for attachment of targeting ligands, viruses were non-genetically modified with pHPMA-ONp polymer. Addition of polymer-coated virus to prostate cells showed significantly reduced transgene expression compared with unmodified virus. To restore infectivity, an a6-integrin binding peptide (-SIKVAV-) derived from laminin was incorporated onto the surface of the polymer-coated viruses. Photon correlation spectroscopic analysis revealed a small increase in the mean diameter of the particles following retargeting. Addition of -SIKVAV-peptide restored virus infectivity of PC-3 cells in a ligand concentration-dependent manner that was significantly improved following removal of unincorporated polymer and peptide. Competition assays using cells preincubated with Ad5 fiber protein or free -SIKVAV-peptide confirmed that entry of retargeted viruses was mediated via the incorporated ligand. Application of retargeted viruses to a panel of human cell lines revealed varying levels of transduction efficiency. Flow cytometric analysis of cells using anti-a6 integrin and anti-b1 integrin antibodies demonstrated that for prostate cells, greater transduction efficiency correlated with higher levels of expression of both integrin subunits. Furthermore with the exception of LNCaP cells, increased a6b1 integrin expression correlated with advanced disease. Intravenous administration of retargeted viruses to tumor-bearing mice resulted in slower plasma clearance and greatly reduced liver tropism, and hence toxicity compared with unmodified virus, while maintaining reporter gene expression in the tumor. The data suggest that YESIKVAVS-retargeted viruses have potential for systemic delivery for the treatment of metastatic disease.

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“…S7). Our results demonstrate that tumors driven by NICD1 in combination with kRas G12D , myrAKT, and Myc exhibit EMT features, a phenotype that may characterize invasive, poorly differentiated carcinoma (42)(43)(44)(45).…”

Section: Gene-expression Profiling Of Tumors Driven By Nicd1 In Combimentioning

confidence: 65%

Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer

Stoyanova

Riedinger

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer.

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Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma

Abstract: Motile prostate cancer cell lines express vimentin. In tissue sections, the presence of vimentin positive tumour cells correlated positively to poorly differentiated cancers and the presence of bone metastases.

Cited by 151 publications

References 30 publications

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Incorporation of a laminin-derived peptide (SIKVAV) on polymer-modified adenovirus permits tumor-specific targeting via α6-integrins

Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer

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