Abstract 168: DDR2 regulates angiogenesis via HSP-90 modulation in ovarian cancer

Abstract

Ovarian cancer is often diagnosed in later stages and patients have low five-year survival. There is a need to develop better therapies for this patient population. Solid tumors like ovarian cancer respond to hypoxia by inducing the sprouting of new blood cells. This process is called angiogenesis. Angiogenesis leads to formation of disordered and immature vessels that precludes efficient drug delivery. Prior work has shown that overexpressing DDR2 in endothelial cells leads to increased angiogenic activity, measured by tube formation and sprouting. We show that DDR2 expression in ovarian cancer tumor cells modulates angiogenic activity in endothelial cells. Human umbilical vein endothelial cells (HUVECs) cultured in conditioned media from DDR2-expressing tumor cells (ES2 shSCRM) have 20% increase in tube length and 18% increase in sprout network area than HUVECs cultured in conditioned media from DDR2-depleted tumor cells (ES2 shDDR2) (P=0.032). This difference in HUVEC angiogenesis is mediated by vascular endothelial growth factor (VEGF). We observed a 16% decrease in VEGF levels in conditioned media from ES2 shDDR2 cells compared to media from ES2 shSCRM cells (P​​<0.0001). DDR2 WT mice bearing ID8 Trp53-/- BRCA2-/- tumors have 53% more CD31+ microvessels than DDR2 KO mice (P​​<0.0001). We also identified that DDR2’s role in angiogenesis is mediated by the Hsp70/90 chaperone machinery. In summary, we have identified that DDR2 regulates angiogenesis in ovarian cancer. Citation Format: Favour A. Akinjiyan, Ritu M. Dave, Gregory Longmore, Katherine C. Fuh. DDR2 regulates angiogenesis via HSP-90 modulation in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 168.

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy

“…Consequently, upregulating vascular adhesion factors in vascular endothelial cells is another effective strategy for increasing immune cell infiltration. Our previous work has found that the mild magnetic heat therapy (MHT) is capable of regulating the intratumoral heat shock protein 70 (HSP70), implying that such a modality can regulate the VEGF expression in solid tumors via HSP-related pathways. − Recently, based on this, our group further designed a type of magnetic nanocatalytic medicines (ZnCoFe 2 O 4 @ZnMnFe 2 O 4 -PBA, ZCMFP) for solid tumor immunotherapy through activating immune cells and regulating vascular permeability . In the acidic TME, the Fe 2+/ Fe 3+ and Mn 2+ released from ZCMFP are able to catalyze ROS production and activate the immunological responses of macrophages and DC through the STING pathway, respectively.…”