22 Feb Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression – Sunila Pradeep, PhD
Sunila Pradeep, PhD
Department of Obstetrics & Gynecology
Medical College of Wisconsin
Dr. Pradeep’s Research
Peritoneal seeding is the most common pathway for the spread of ovarian cancer. Because 90% of ovarian cancers are surface epithelial carcinomas, the tumor cells are able to slough off the ovary and enter the peritoneal circulation, thereby seeding multiple sites in the abdominal cavity. Despite the widely-held view that epithelial ovarian cancer metastasizes via peritoneal seeding, the distribution of ovarian metastasis was peculiar in that the ovarian cancer cells gravitated toward the omentum, an apron tissue over the abdomen as the preferred site of metastasis. The omentum is composed of fatty tissue interspersed with immune cell aggregates or “milky spots”, consisting of macrophages, leukocytes, stem and progenitor cells, fibroblasts, and endothelial cells. It is known that disseminated tumor cells adhere to milky spots within hours, and milky spots are sources of cytokines and chemokines sites that facilitate local proliferation of tumor cells, and maturation of macrophages. Given the highly metastatic nature of ovarian cancer, we have an interest in understanding the mechanisms of how immune cells facilitate omental metastasis of ovarian cancer cells.
Our previous work at MD Anderson has demonstrated increased expression of neuregulin 1 (NRG1), the binding partner of ErbB3 (Erb-B2 Receptor Tyrosine Kinase 3), promotes homing of ovarian cancer cells to the omentum (Pradeep et al., Cancer Cell, 2014). In my lab at MCW, we will investigate how adipocytes reprogram the immune cells in omentum to enhance ovarian cancer cell progression and metastasis. We believe that these new mechanisms will offer new options for therapy targeting ovarian cancer metastasis.