Role of CD70 in pathogenesis of ovarian cancer cell metastasis

Abstract

American Cancer Society identifying ovarian carcinoma as the gynecologic malignancy with the highest case-to-fatality. Ovarian carcinoma metastasizes either by direct extension from the ovarian/fallopian tumor to neighboring organs (bladder/colon) or when cancer cells detach from the primary tumor. Exfoliated tumor cells are transported throughout the peritoneum by physiological peritoneal fluid and disseminate within the abdominal cavity. Extensive seeding of the peritoneal cavity by tumor cells is often associated with ascites, particularly in advanced, high-grade serous carcinomas. CD70 (encoded by the TNFSF7 gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. CD70 is over expressed in tumor cells of various solid cancers including ovarian carcinoma, recently reported the role of CD70 expression as a predictive marker of resistance to chemotherapy in ovarian cancers. We evaluated the expression of CD70 level in the pathogenesis of metastasis ovarian cancer cell. Seventy five tissue samples from metastatic ovarian carcinoma were evaluated by quantitative real-time PCR for CD70 and statistical analyses were performed using the Mann-Whitney test. Further, humanized anti-CD70 antibodies were investigated in xenograft mice models of ovarian cancer. Increasing expression of CD70 level was associated with increased risks for disease progression (HR = 1.04; 95% CI, 1.03 to 1.14) and death (HR = 1.13; 95% CI, 1.09 to 1.2). expression of CD70 was associated with a worse PFS and OS compared with non- expression of CD70 carcinomas. Furthermore, humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of ovarian cancer cell.