PMID- 19671672 OWN - NLM STAT- MEDLINE DCOM- 20100106 LR - 20181201 IS - 1557-3125 (Electronic) IS - 1541-7786 (Linking) VI - 7 IP - 8 DP - 2009 Aug TI - Differential influence of normal and cancer-associated fibroblasts on the growth of human epithelial cells in an in vitro cocultivation model of prostate cancer. PG - 1212-23 LID - 10.1158/1541-7786.MCR-09-0073 [doi] AB - The prostate is composed of a number of different cell populations. The interaction between them is crucial for the development and proper function of the prostate. However, the effect of the molecular cross talk between these cells in the course of carcinogenesis is still unclear. Employing an approach wherein immortalized epithelial cells and immortalized human fibroblasts were cocultured, we show that normal associated fibroblasts (NAF) and cancer-associated fibroblasts (CAF) differentially influenced the growth and proliferation of immortalized human prostate epithelial cells. Whereas NAFs inhibited the growth of immortalized epithelial cells but promoted the growth of metastatic PC-3 cells, CAFs promoted the growth of immortalized epithelial cells but not of PC-3. Cytokine arrays revealed that NAFs secreted higher levels of tumor necrosis factor-alpha compared with CAFs whereas CAFs secreted higher levels of interleukin-6 (IL-6) compared with NAFs. The growth-inhibiting effects of NAFs were counteracted by the addition of IL-6, and the growth-promoting effects exerted by the CAFs were counteracted by tumor necrosis factor-alpha. Furthermore, CAFs induced the migration of endothelial cells in an IL-6-dependent manner. Here, we show that normal fibroblast cells have a protective function at very early stages of carcinogenesis by preventing immortalized epithelial cells from proliferating and forming new blood vessels whereas CAFs aid immortalized epithelial cells to further develop. FAU - Paland, Nicole AU - Paland N AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Herzl, 1, Rehovot 76303, Israel. FAU - Kamer, Iris AU - Kamer I FAU - Kogan-Sakin, Ira AU - Kogan-Sakin I FAU - Madar, Shalom AU - Madar S FAU - Goldfinger, Naomi AU - Goldfinger N FAU - Rotter, Varda AU - Rotter V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090811 PL - United States TA - Mol Cancer Res JT - Molecular cancer research : MCR JID - 101150042 RN - 0 (Androgens) RN - 0 (Culture Media, Conditioned) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Androgens/pharmacology MH - Cell Line, Transformed MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Coculture Techniques MH - Culture Media, Conditioned/pharmacology MH - Epithelial Cells/*cytology/drug effects MH - Fibroblasts/drug effects/metabolism/*pathology MH - Humans MH - Interleukin-6/metabolism/pharmacology MH - Male MH - *Models, Biological MH - Prostatic Neoplasms/*pathology MH - Tumor Necrosis Factor-alpha/metabolism/pharmacology EDAT- 2009/08/13 09:00 MHDA- 2010/01/07 06:00 CRDT- 2009/08/13 09:00 PHST- 2009/08/13 09:00 [entrez] PHST- 2009/08/13 09:00 [pubmed] PHST- 2010/01/07 06:00 [medline] AID - 1541-7786.MCR-09-0073 [pii] AID - 10.1158/1541-7786.MCR-09-0073 [doi] PST - ppublish SO - Mol Cancer Res. 2009 Aug;7(8):1212-23. doi: 10.1158/1541-7786.MCR-09-0073. Epub 2009 Aug 11.