Inhibition of MCF-7 breast cancer cell proliferation by MCF-10A breast epithelial cells in coculture.
A coculture system was developed to investigate the interactions between MCF-10A breast epithelial cells and MCF-7 breast cancer cells stably expressing the green fluorescent protein (MCF-7-GFP). Studies with this MCF-10A/MCF-7-GFP coculture system on microtiter plates and on reconstituted basement membrane (Matrigel), revealed paracrine inhibition of MCF-7-GFP cell proliferation. Epidermal growth factor, which in monocultures modestly enhanced MCF-7-GFP and markedly increased MCF-10A cell proliferation, greatly inhibited MCF-7-GFP cell proliferation in MCF-10A/MCF-7-GFP cocultures. 17beta-Estradiol, which stimulated MCF-7-GFP but not MCF-10A cell proliferation in monoculture, inhibited MCF-7-GFP cell proliferation in MCF-10A/MCF-7-GFP cocultures, an effect that was blocked by the antiestrogen, ICI 182,780. On Matrigel, complex MCF-10A/MCF-7-GFP cellular interactions were observed in real time that resulted in the formation of acinus-like structures. These results indicate a role of normal epithelial cells in inhibiting tumor-cell proliferation and demonstrate the utility of this coculture system as a model of early paracrine control of breast cancer.
Spink
Barbara C
BC
Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201-0509, USA. spink@wadsworth.org
Cole
Richard W
RW
Katz
Barbara H
BH
Gierthy
John F
JF
Bradley
Laurie M
LM
Spink
David C
DC
D001940:Breast / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003094:Collagen; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007633:Keratins / Q000378:metabolism; D007797:Laminin; D019899:Paracrine Communication / Q000187:drug effects; D011509:Proteoglycans; D015843:Serpins / Q000378:metabolism; D013997:Time Factors
D004338:Drug Combinations; D006133:Growth Substances; D007797:Laminin; D011509:Proteoglycans; C085344:SERPIN-B5; D015843:Serpins; C059485:matrigel; D000077267:Fulvestrant; D004958:Estradiol; D007633:Keratins; D003094:Collagen