Isolation and characterization of stroma from mouse mammary glands: Toward the development of a second generation stroma-derived matrix-gel
Fischer, John Adams
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It is now understood that environmental factors are capable of modulating not only gene expression but also the surrounding environment of cells. This extracellular environment varies in composition and architecture at different sites in the body in an organ and tissue specific manner. Recently, it has been shown that the extracellular environment, composed of supporting extracellular matrix proteins as well as associated stromal cells, is a target of chemopreventative therapies designed to alter its composition in a way that makes it non-permissive for the growth and progression of tumors. So far, the most promising therapies are those that involve modification of the stroma to produce an anti-angiogenic environment to reduce the ability of tumor-associated blood vessels to grow and invade normal tissue. Nowhere in the body is this more evident than in the mammary gland. The mammary gland represents a site of continual postnatal remodeling of the extracellular environment. This remodeling occurs in response to hormonal signals during the reproductive cycles and pregnancy. It is thought that due to constant remodeling and differentiation of mammary epithelial structures the mammary gland represents a highly sensitive target for agents responsible for the transformation of cells. In addition to transformation of epithelial cells, tumor progression can only occur to a certain extent until it requires a new and ever increasing supply of blood vasculature. Although many extracellular factors have been implicated in the process of angiogenesis, there does not exist to be a clear method for obtaining samples of normal stroma for characterization in a diagnostic setting. The goal of this thesis is to develop a protocol for the extraction of normal mammary gland extracellular matrix proteins that can be isolated, characterized and utilized in bioassays to determine their relative potential for either promoting or suppressing the growth of tumors.