Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium.
MICHIGAN STATE UNIV EAST LANSING
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Specific extracellular matrix ECM proteins and their cellular receptors integrins are required for normal mammary gland morphogenesis and differentiation, while their expression is dramatically altered during tumorigenesis. It is not clear how ECM proteins affect breast tumor growth, however. We have examined the effects of five ECM proteins on two estrogen Eregulated events, proliferation and induction of progesterone receptor PgR, using estrogen receptor positive MCF-7, T47D or negative MDA MB23 1 breast cancer cells. In the presence of serum, E enhanced proliferation of MCF-7 or T47D cells on collagen I, collagen IV, fibronectin, and vitronectin, but was less effective on laminin. MDA MB23 1 cells were not E-responsive on any ECM protein in the presence or absence of serum. MCF-7 cell PgR induction was enhanced by E on all ECM proteins in the presence or absence of serum, though response on laminin was weaker. In the absence of serum, MCF-7 and T47D cells proliferated in response to E maximally on collagen I, followed by fibronectin or vitronectin. However, the growth factors, ICIF- and ECIF, were required for E-induced proliferation and PgR induction in the absence of serum. These results have demonstrated that laminin can inhibit, while collagen I, fibronectin or vitronectin may enhance E-mediated cell proliferation and PgR induction. Since specific ECM proteins may confer and others inhibit E-responsiveness in breast cancer cells, therapeutic strategies may be designed to alter the ECM or integrin- ECM adhesion in the tumor microenvironment to prevent tumor growth and spreading.
- Anatomy and Physiology
- Medicine and Medical Research