Vol 13: Induction of integrin 2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture.Report as inadecuate



 Vol 13: Induction of integrin 2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture.


Vol 13: Induction of integrin 2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 13: Induction of integrin 2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture.
This article is from Molecular Cancer, volume 13.AbstractBackground: Prostate cancer PCa bone metastasis can be markedly enhanced by increased receptor activator of NF kappa-B ligand RANKL expression in PCa cells. Molecular mechanisms that account for the increased predilection of PCa for bone include increased bone turnover, promotion of PCa cell growth and survival in the bone environment, and recruitment of bystander dormant cells to participate in bone metastasis. The current study tests the hypothesis that PCa cells acquire high adhesion to bone matrix proteins, which controls PCa bone colonization, under the RANKL-RANK and AR axes. Methods: We used a highly bone metastatic RANKL-overexpressing LNCaP PCa cell line, LNCaPRANKL, as a model to pursue the molecular mechanisms underlying the increased adhesion of PCa cells to collagens. A three-dimensional 3-D suspension PCa organoid model was developed. The functions of integrin α2 in cell adhesion and survival were evaluated by flow cytometry and western blot. AR expression and functionality were compared in 2-D monolayer versus 3-D suspension cultures using AR promoter- and PSA promoter-luciferase activity. AR role in cell adhesion was assessed using an adhesion assay. Results: LNCaPRANKL cells were shown to adhere tightly to ColI matrix through increased α2 integrin expression. This increased adhesion, concomitant with activation of the FAK and Akt pathways, was further enhanced by culturing LNCaPRANKL cells in 3-D suspension. Under the influence of 3-D suspension culture, AR was restored in LNCaPRANKL cells via downregulation of AP-4 transcription factor, and supported increased α2 integrin expression and adhesion to ColI. Conclusion: 3-D suspension culture and in vivo PCa tumor growth restore AR through downregulation of AP-4, enhancing integrin α2 expression and adhesion to ColI which is rich in bone matrices. The interactions of PCa with ColI, mediated by integrin α2 and AR expression, could be a key molecular event accounting for PCa bone metastasis. Electronic supplementary material: The online version of this article doi:10.1186-1476-4598-13-208 contains supplementary material, which is available to authorized users.



Author: Ziaee, Shabnam; Chung, Leland WK

Source: https://archive.org/







Related documents