Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch
Annual rept. Jul 2014-Jul 2015
MAINE MEDICAL CENTER PORTLAND
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Ovarian cancer is among the most lethal forms of gynecological malignancies with limited durable responses observed following front line treatment for late stage recurrent disease. We have proposed to assess the role of alpha10beta1 on tumor growth and chemosensitivity in vivo. We have made significant progress towards the completion of the overall goals of this project during this initial funding period. In particular, we, have characterized stromal cell infiltration of ovarian tumors and have shown extensive infiltration of tumor associated blood vessels as well as fibroblasts which can express high levels of protumorigenic cytokines. Targeting the HU177 collagen epitope recognized by a alpha10beta1 significantly reduced angiogenesis and fibroblast infiltration. Interestingly, while reducing expression of alpha10beta1 can inhibit fibroblast migration on denatured collagen, it failed to reduce cell adhesion. Moreover a peptide antagonist of alpha10beta1 may inhibit ovarian tumor growth in vivo. Finally, our studies suggest that the number and size of ovarian tumors was reduced in transgenic mice that lack alpha10beta1 and a reduction in stromal cell infiltration was observed in tumors from alpha10beta1 null mice. Collectively, our new findings support the hypothesis that alpha10beta1 plays a role in regulating stromal cell behavior and ovarian tumor growth.
- Medicine and Medical Research