Influence of the Metastatic Microenvironment on Stem-like Human Breast Cancer Cells

Ashkan Sadri, The University of Western Ontario

Abstract

Ninety percent of breast cancer-related mortalities result from metastasis. We have previously demonstrated that stem-like ALDHhiCD44+ breast cancer cells are critical for metastasis, and preferentially target the lung and bone marrow (BM). We hypothesize organ tropism occurs through promotion of the ALDHhiCD44+ phenotype. Using a 2D ex vivo model, lung and BM conditioned media (CM) were utilized to assess their influence on stem-like phenotype and behavior. Exposure of human breast cancer cells to lung-CM significantly decreased the proportion of cells with a stem-like ALDHhiCD44+ phenotype, decreased expression of cancer stem cell (CSC)-related genes, and increased gene expression related to migration (p