Anirban K. Mitra, PhD

Role of reciprocal interactions between cancer cells and their microenvironment in regulation of ovarian cancer metastasis.

Ovarian cancer is the most lethal of all gynecologic malignancies primarily because most ovarian cancer patients present with extensive metastasis when they are first diagnosed. There has been no significant improvement in survival rates over the last three decades. Metastasis is responsible for most cancer related deaths and is one of the least understood aspects of the disease. Therefore, it is imperative to understand the process of ovarian cancer metastasis and devise new therapies targeting metastatic disease. Ovarian cancer has a unique metastasis, which rarely takes the hematogenous route. During the process of abdominal dissemination, the cancer cells floating in the peritoneal fluid have to attach to the mesothelial cells lining the peritoneal organs and interact with the microenvironment at the site of metastasis to successfully establish metastatic colonies. The cross talk between the cancer cells with the microenvironment of the metastasis site and the regulation of the initial steps of colonization is crucial and largely unknown.

My laboratory seeks to understand the paracrine and juxtacrine interactions between cancer cells and their microenvironment that regulate metastatic colonization in ovarian cancer. We are using in vitro organotypic 3D culture models, live 3D time lapse microscopy and mouse xenograft models of metastasis along with cell and molecular biological approaches to study the reciprocal interactions between the metastasizing cancer cells with their microenvironment at the site of metastasis. We are specifically interested in the regulation of key microRNAs and transcription factors by these paracrine/juxtacrine interactions and the mechanism by which they drive metastatic colonization in ovarian cancer. We have developed novel assays like a plug homing assay and a 3D time-lapse confocal microscopy based assay for co-invasion of cancer cells along with stromal cells.