Roles of the extracellular matrix in driving metastasis and chemoresistance

Speaker: Dr Madeleine Oudin, Department of Biomedical Engineering, Tufts University, Massachusetts.

Host: Matthias Krause

 

The extracellular matrix (ECM) is a major component of the tumor microenvironment, where it can support cellular growth, promote local invasion from the primary tumor, and contribute to metastatic outgrowth in distant sites. Our research focuses on understanding how individual ECM proteins upregulated in metastatic breast tumors drive local invasion and support metastasis. Obesity is a systemic disease that causes chronic inflammation which can lead to ECM deposition in mammary tissues and is associated with increased metastasis. By performing proteomics of the obese mammary gland ECM and comparing it to the tumor ECM, we identified Collagen VI as a novel driver of breast cancer metastasis. Furthermore, we investigated how ECM proteins upregulated in metastatic tumors impact response to chemotherapy, drugs commonly used to treat metastatic breast cancer. We find that individual ECM proteins differentially impact response to drugs and that chemotherapy treatment alters the ECM composition of breast tumors, suggesting that the ECM may a play in chemotherapy-induced metastasis. Overall, these studies further support the importance of the ECM as a key regulator of metastasis and drug resistance.