Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Alison Allan

Abstract

The majority of breast cancer deaths occur due to metastasis, with the most common site of breast cancer metastasis being bone. Previous work in our laboratory has established that stem-like breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and expression of a CD44+CD24- phenotype have enhanced metastatic capacity. This study tested the hypothesis that bone-derived osteopontin (OPN) promotes the migration and stem-like behavior of breast cancer cells. We demonstrate that bone- derived OPN promotes migration, tumorsphere-forming ability and colony-forming ability of whole population and ALDHhiCD44+CD24- breast cancer cells in bone marrow- conditioned media (an ex vivo representation of the bone microenvironment). We observed that cell surface receptors CD44 and RGD-dependent integrins facilitate these behaviors via OPN, potentially through activation of WNK-1, PRAS40 and HSP60 signaling in breast cancer cells. Our analysis of the interactions between bone-derived OPN and breast cancer cells provides valuable insight regarding breast cancer cell metastasis to bone.


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