A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia.
Here we report the characterization of an SV40 large-T antigen-immortalized stromal cell line, WPMY-1, derived from the same prostate as our previously described epithelial cell lines. The WPMY-1 cells were determined to be myofibroblasts on the basis of co-expression of smooth muscle alpha-actin and vimentin. They also show positive staining for androgen receptor, large-T antigen, and positive but heterogeneous staining for p53 and pRb. Their growth is stimulated by the synthetic androgen mibolerone to 145% of control (100%). Platelet-derived growth factor BB, epidermal growth factor and basic fibroblast growth factor, at 10 ng/ml, stimulated growth to 138, 143 and 146% of control, respectively. Transforming growth factor-beta, at 10 ng/ml, inhibited serum-induced growth to 65% of control in the presence of 1% serum, and bFGF-induced growth to 30% of control. A serum-free medium was developed for optimal growth of WPMY-1 cells. They show anchorage-independent growth in soft agar. Studies on paracrine interactions show that myofibroblast-conditioned medium causes a marked inhibition of growth in WPE1-10 cells, while conditioned medium from WPE1-10 prostatic epithelial cells caused only a small increase in the growth of WPMY-1 cells. WPMY-1 cells secrete very low levels of MMP-9 but high levels of MMP-2, markedly higher than the epithelial cells. These epithelial and myofibroblast cell lines, derived from the same prostate, provide novel and useful models for studies on paracrine stromal-epithelial interactions in carcinogenesis, tumor progression, prevention and treatment of prostate cancer and benign prostatic hyperplasia.
Webber
M M
MM
Departments of Zoology and Medicine, and Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824-1312, USA.
Trakul
N
N
Thraves
P S
PS
Bello-DeOcampo
D
D
Chu
W W
WW
Storto
P D
PD
Huard
T K
TK
Rhim
J S
JS
Williams
D E
DE
D000199:Actins / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017364:Collagenases / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011467:Prostate / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D000943:Antigens, Differentiation; D000957:Antigens, Viral, Tumor; D017077:Culture Media, Conditioned; D005353:Fibronectins; D006133:Growth Substances; D007527:Isoenzymes; D014746:Vimentin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9