Figure 3.

“Normalization” of the tumor microenvironment. If matrix components essential to tissue homeostasis are reestablished at normal tissue levels, either through exogenous administration or re-expression, the tumor microenvironment is attenuated. For example, TIMP-2 treatment would restrict MMP-mediated destruction of ECM structural and biochemical components; reduce tumor-associated angiogenesis; and directly alter tumor cell gene expression. Further, return of the microenvironment towards a more homeostatic balance, or “normalization” of the ECM, would be accompanied by a reduction in activated fibroblasts (cancer-associated fibroblasts), inflammatory cell infiltration and tumor-associated angiogenesis. Cumulatively, these pluripotent effects would reduce tumor growth capacity and enhanced sensitivity to chemo/radiation therapy.