Document Detail

Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells.
MedLine Citation:
PMID:  20665531     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Preferential bony metastasis of human prostate cancer (PCa) cells contributes to disease mortality and morbidity. Local factors in bone stromal extracellular matrix microenvironment affect tumor growth through paracrine interactions between tumor and stromal cells.
METHODS: Using co-culture and medium transfer, we used several methods to assess interactions between PCa and bone stromal cells using three PCa cell lines: PC3, LNCaP, and the LNCaP derivative, C4-2B.
RESULTS: Co-culture of LNCaP and C4-2B cells with bone marrow stromal cell lines, HS27a and HS5, decreased cell number, as did culture with conditioned medium (CM) harvested from these two cell lines suggesting a soluble paracrine factor was responsible. PC3 cell growth was unaffected. CM harvested from bone stromal cell lines triggered apoptosis in LNCaP and C4-2B cell lines, but not in PC3 cells. Surviving C4-2B cells grown in bone stromal cell CM over several days were growth arrested, suggesting presence of a growth inhibitor. Apoptosis induced by CM was dose-dependent. Flow cytometry demonstrated that over a 5-day culture period in stromal cell CM, LNCaP, and C4-2B cell lines, but not PC3 cells, underwent greater apoptosis than parallel cultures in SF medium. The LNCaP and C4-2B cells showed morphology and biomarker expression consistent with transdifferentiation towards a neuroendocrine phenotype after exposure to stromal cell CM.
CONCLUSIONS: The reactive bone stromal microenvironment initially is hostile to PCa cells producing widespread apoptosis. Activation of transdifferentiation in a subset of apoptotic resistant cells may support phenotypic adaptation during disease progression in bone, eventually favoring lethal disease.
Chu Zhang; Mehrnoosh Soori; Fayth L Miles; Robert A Sikes; Daniel D Carson; Leland W K Chung; Mary C Farach-Carson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Prostate     Volume:  71     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-24     Completed Date:  2011-01-24     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  157-67     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
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MeSH Terms
Apoptosis / physiology*
Blotting, Western
Bone Marrow Cells / metabolism*,  pathology
Bone Neoplasms / metabolism,  secondary
Cell Differentiation / physiology*
Cell Growth Processes / physiology
Coculture Techniques
Culture Media, Conditioned
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Neoplasms, Hormone-Dependent / metabolism,  pathology
Neuroendocrine Tumors / metabolism,  pathology*
Prostatic Neoplasms / metabolism,  pathology*
Stromal Cells / metabolism,  pathology
Grant Support
P01 CA098912/CA/NCI NIH HHS; P01 CA098912/CA/NCI NIH HHS; P01 CA098912-01A10002/CA/NCI NIH HHS; P01 CA098912-068184/CA/NCI NIH HHS; P20 RR016472/RR/NCRR NIH HHS; P20 RR016472-086384/RR/NCRR NIH HHS; P20 RR016472-096351/RR/NCRR NIH HHS; P20-RR016472/RR/NCRR NIH HHS
Reg. No./Substance:
0/Culture Media, Conditioned

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