Ovarian Cancer Cell Exosome Interactions with Platelets: A role for the Novel Transmembrane Protein SUSD2

Ovarian cancer (OvCa) is the deadliest gynecologic cancer and ranks as the seventh‐leading cause of cancer death among women. OvCa can metastasize without the aid of the circulatory or lymphatic system by traveling through the peritoneal fluid (ascites), adhering to the mesothelial lining, and spreading to neighboring organs. Furthermore, OvCa tumors can hijack platelets as a means to evade immune responses and medicinal therapies. Recently, a novel tumor cell surface protein, Sushi Domain Containing 2 (SUSD2), was correlated with increased OvCa survival rates, as well as lowered platelet adhesion. Given that OvCa tumor cells are bathed in relatively minimal levels of platelets in the ascites, we hypothesized that OvCa cells can interact with platelets distally via released exosomes, and that exosome‐platelet interaction can be inhibited by abundant SUSD2 presence on the tumor cells. To test this hypothesis, exosomes were harvested from OvCa‐derived cell line media supernatant, isolated via differential ultracentrifugation, and verified via Western blotting for exosome‐specific markers and flow cytometric gating on exosome‐sized cell particles. Exosomes derived from SUSD2‐knockdown cell lines were secreted at significantly higher amounts compared to cells with higher levels of SUSD2 expression. Similarly, exosomes from SUSD2‐knockdown cells had a more pronounced positive effect on agonist‐induced platelet activation as measured by GPIIb/IIIa integrin conformational activation, as well as increased platelet spreading on fibrinogen. The results suggest a mechanistic role of SUSD2 in OvCa exosome production and exosome‐platelet communication, and a link between cancer cell and platelet interaction that does not require proximal contact. Support or Funding Information Research was supported in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103443), as well as funding from the National Science Foundation/EPSCoR program [IIA‐1355423], the state of South Dakota, the Cynthia Ballentine‐Roesler Memorial Fund, and an undergraduate fellowship from the American Physiological Society. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .