Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch
Technical Report,15 Jul 2014,14 Jul 2016
Maine Medical Center Portland United States
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Ovarian cancer is the most lethal form of gynecological malignancies with limited durable responses observed following frontline treatment for late stage recurrent disease. We proposed to assess the role of alpha 10 beta 1 on tumor growth and chemosensitivity in vivo. We have made significant progress towards the completion of the overall goals of this project. 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 pro-tumorigenic cytokines. Targeting the HU177 collagen epitope recognized by alpha 10 beta 1 significantly reduced angiogenesis and fibroblast infiltration. Interestingly, while reducing expression of alpha 10 beta 1 can inhibit fibroblast migration on denatured collagen it failed to reduce cell adhesion. Moreover a peptide antagonist of alpha 10 beta 1 may inhibit ovarian tumor growth in vivo. Our studies suggest that the number and size of ovarian tumors was reduced in transgenic mice that lack alpha 10 beta 1 and a reduction in stromal cell infiltration was observed in tumors from alpha 10 beta 1 null mice. Moreover, our data suggest the presence of fibroblast that express integrin alpha 10 beta 1 may provide a growth advantage to ovarian tumors in vivo. Collectively, our new findings support the hypothesis that alpha 10 beta 1 plays a role in regulating stromal cell behavior and ovarian tumor growth.
- Medicine and Medical Research