A Biophysical Perspective of Breast Cancer Metastasis and Treatment Resistance

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Investigator: Valerie M. Weaver, PhD
Sponsor: U.S. Army Medical Research Acquisition Activity

Location(s): United States

Description

Apoptosis resistance regulates the pathogenesis, and treatment response of breast tumors. Despite concerted effort towards understanding the molecular basis for apoptosis resistance in breast tumors, progress in this area has been frustratingly slow. Lack of advancement may be attributed in part to the current cell autonomous view of breast cancer etiology and treatment responsiveness. What we now know is that the organ microenvironment can and does regulate the therapeutic responsiveness of metastatic tumors (Taylor et al., 2000, Zahir et al., 2004), and that stromal-epithelial interactions influence mammary gland development, tissue homeostasis and breast tumor progression (Unger and Weaver, 2003). Alterations in the mammary gland ECM correlate with changes in mammary differentiation, involution (apoptosis) and tumor progression, and culture experiments clearly show that the stromal ECM can modulate mammary epithelial cell (MEC) growth, differentiation and survival and alter apoptotic responsiveness (Zahir et al., 2004, Truong et al., 2003, Lewis, Truong and Schwartz, 2002). How the stroma promotes apoptosis-resistant breast tumors remains unclear.