Inhibition of MCF‐7 breast cancer cell proliferation by MCF‐10A breast epithelial cells in coculture

Authors:
  • RCRichard W. Cole
    Richard W. Cole
  • BKBarbara H. Katz
    Barbara H. Katz
  • JGJohn F. Gierthy
    John F. Gierthy
  • LBLaurie M. Bradley
    Laurie M. Bradley

Abstract
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. 17β‐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.

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