More on CAFs and Breast Cancer
Scientists at Perelman School of Medicine of the University of Pennsylvania and the Wistar Institute reported that breast cancer subtype-specific changes occur in CAFs derived from breast cancer. Lead author Julia Tchou, M.D., Ph.D. of Penn and Wistar colleagues asked whether the reported gene expression profile differences between CAFs in breast cancer stroma and normal breast fibroblasts could be stratified based on tumor subtypes.
The investigators noted that previous gene expression profile analyses comparing CAFs and fibroblasts derived from matched normal adjacent breast tissues demonstrated significant differences between the CAF and their normal counterparts. But to their knowledge, they said, no prior studies addressed whether CAFs derived from various breast cancer subtypes harbored subtype-specific gene expression signatures.
In their study, the investigators compared gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main breast cancer subtypes: ER+, triple negative (TNBC), and Her2+.
The investigators observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling.
To explore whether CAFs derived from various breast cancer subtypes can differentially enhance the migratory phenotype of breast cancer cells, the researchers compared the migration of breast cancer cells cultured in the presence or absence of CAFs isolated from ER+, Her2+, and TNBC cells. As their expression profile results predicted, CAFs derived from Her2+ breast cancer significantly enhanced the migration of T47D.
In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer, they said.
And as noted in the first part of this two part series focusing on cancer stromal drug targets, one potential stromal drug target is FAP (fibroblast activation protein), a cell surface serine protease selectively expressed on tumor-associated fibroblasts and other mesenchymal stromal cells in epithelial tumors. Dr. Tchou told GEN that FAP represents an exciting potential target in breast cancer. “Existing and future FAP directed therapy may be explored in conjunction with conventional chemotherapy to augment efficacy of existing therapy against breast cancer,” she said.