Research

QBCF Strategic Grants Program

Research Factsheet

DR. MORAG PARK

McGILL UNIVERSITY, MONTRÉAL

PROJECT TITLE Gene expression and phenotypic characterization of circulating tumor cells: Towards an understanding of the seeds of metastasis

PRINCIPAL INVESTIGATOR Dr. Morag Park

INSTITUTE McGill University

CO-APPLICANTS

Dr. Catalin Mihalcioiu, McGill University • Dr. Michael T. Hallet, McGill University • Dr. Michael Sebag, McGill University • Dr. Richard Kremmer, McGill University • Dr. Giovanni (John) Di Battista, McGill University

TOTAL RESEARCH BUDGET $449,998

RESEARCH SUMMARY*:

In breast cancer, poor outcome is generally due to the spread of cancer cells to distant organs and their subsequent growth at these sites. As cancer cells migrate from the primary tumor to other sites, they must travel through the circulation, where they are known as circulating

tumor cells (CTCs). Previously these cells have been difficult to study; they are relatively rare, and techniques for their isolation from peripheral blood samples have been inefficient. To collect large numbers of CTCs, we have adapted the technology of whole blood volume aphaeresis, in which the entire blood volume of a patient is circulated through a collection system that traps cells traveling in the bloodstream. We propose that within the CTC population, there is a group of cells (circulating tumor-initiating cells, or CTICs) that is both resistant to chemotherapy and capable of colonizing and forming tumors in other tissues and organs in the body, and that these may be the cause of disease recurrence. We will isolate CTCs from a group of patients with early-stage breast cancer and study both the overall CTC population and the CTIC subgroup, which can be isolated in part due to a distinct set of marker proteins. We will use microarray technology to discover the sets of genes transcribed in each CTC subgroup from individual patients, and correlate this data with patient outcome, response to treatment, and the expression of selected marker proteins in patient-matched tissue samples (primary tumor, lymph nodes, bone marrow).

We will also investigate the ability of CTC subsets to form tumors in the mammary fat pads of immune-deficient mice, where one can implant human tumor cells and observe if and how they grow. Coupling detailed molecular characterization of CTCs with an understanding of their contribution to disease course is expected to lead to the development of novel prognostic tools and treatment protocols, and the identification of new targets for pharmacological intervention.

* This document is a non-scientific summary.