Abstract 163: Regulation of periostin by DDR2 in cancer-associated fibroblasts controls tumor invasion and metastasis in ovarian cancer

Abstract

Ovarian cancer has the highest mortality of all gynecological malignancies. As such, there is a need to decipher molecular mechanisms that underlie tumor metastasis in ovarian cancer. Increased expression of receptor tyrosine kinase, DDR2, has been associated with worse patient survival. Identifying downstream targets of DDR2may allow specific modulation of ovarian cancer metastatic pathways with few off-target effects. Additionally, stromal cells play a critical role in metastasis. The crosstalk between tumor and stromal cells cans hift the balance between tumor progression or inhibition. We identified periostin to be highly expressed by fibroblasts expressing DDR2compared to fibroblasts without DDR2(Fold change=2.0, P=0.03).We show that DDR2regulates periostin in ovarian cancer associated fibroblast (CAFs). DDR2and periostin expression in the CAFs leads to512% increase in mesothelial cell clearance ratio(P=0.0004) and matrigel invasion(612vs 193invading cells/hpf, P<0.0001). Mice injected withCAFs expressing periostin as well as ovarian cancer tumor cells have 72% increased tumor burden compared to mice with CAFs that do not express periostin (P=0.006). High periostin expression in CAFs leads to decreased T-cell proliferation and cytotoxicity. We validate periostin as a marker for patient outcome in ovarian cancer patients. Patients with high periostin expression have worse overall survival thant hose with low periostin expression. Mapping regulatory networks involved in tumor initiation and progression is important for identification of novel therapeutic targets. Citation Format: Favour A. Akinjiyan, Ritu M. Dave, Katherine C. Fuh. Regulation of periostin by DDR2 in cancer-associated fibroblasts controls tumor invasion and metastasis 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 163.