Podocalyxin as a basal like breast cancer stem cell marker
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Breast cancers are heterogeneous in their clinical course and their response to therapy. This is largely due to differences in their underlying biology, with at least five different types of breast cancers being recognized through gene expression and pathology studies. Of these, basal-like is one of the most aggressive forms of breast cancer is associated with poor prognosis and a high risk of metastases. One of the current prevailing theories in breast cancer recurrence and metastasis is that metastases may develop from a small population of breast cancer stem cells that may be resistant to established therapies. However this theory is not without controversy. In support of this theory, populations of cancer cells can be identified in breast cancers and cancer cell lines that have some stem cell characteristics such as prolonged growth capacity in tissue culture and the ability (albeit limited) to reestablish the phenotypic heterogeneity of the primary tumor. Recent studies have shown such cells to be basal-like in phenotype and often to be associated with reduced expression of the gene BRCA1. Our new and unpublished studies implicate another gene, podocalyxin as a potential regulator of the basal-like phenotype. Podocalyxin is a cell surface glycoprotein structurally related to the vascular endothelium marker CD34 that is expressed on the surface of a wide range of cells including kidney podocytes, vascular endothelial cells, hematopoietic stem cells, and platelets. Podocalyxin is best characterized in the kidney where it functions as an anti-adhesion molecule that maintains open filtration pathways between neighboring podocyte foot processes.
 
 
 
 
 
 
 
 We will use complementary cellular and molecular approaches using mouse models to establish a role for podocalyxin in basal-like breast cancer and breast cancer stem cell development. The expression of the podocalyxin gene in established breast cancer cell lines will be modulated. This will allow us to determine if increased expression leads to a basal-like phenotype with an increased population of cancer stem cells. Likewise, we will test whether decreased expression leads to a reversal of this phenotype. The subsequent aggressiveness of these “cancer stem cells” will be determined by assessing their growth as tumors in mice.
 
 
 
 
 
 
 
 This project focuses on trying to establish the role of podocalyxin signaling in the development of basal-like breast cancer and breast cancer stem cells (CSCs) with the intermediate goal of identifying underlying molecular mechanisms and future goal of identifying novel targets for the treatment of this devastating disease. Basal-like breast cancer accounts for around 15% of all breast cancers. However, basal-like breast cancers arising in premenopausal African American women account for nearly 40% of breast cancers arising in this population. If our hypothesis is correct we will have identified a signaling pathway that represents a potential novel therapeutic target.