The leading cause of breast cancer-associated death is metastasis. During metastasis, tumor cells metastasize from primary tumors to distant organs via the circulatory and lymphatic systems. However, in 80% of solid tumors, metastasis via the lymphatic system precedes metastasis via the vascular system. There is a lot of information about metastasis through the circulatory system. However, not much information is available about the tumor cell dissemination through the lymphatic system or the lymphatic microenvironment that aids in this process in breast cancer metastasis. In addition, the molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known.
This project aims to determine why and how tumor cells metastasize to the lymphatic system. The proposal is based on the hypothesis that active migration is needed for tumor cells to spread via the lymphatic vessels. Thus, finding and understanding the molecules that contribute to this can be a breakthrough for breast cancer metastasis therapy.
The goals of this thesis are to 1) Examine the molecular, genetic, and proteomic characteristics of circulatory tumor cells and compare these to the primary tumor and lung metastasis, 2) Examine the role of Toll-like receptors in tumor cell migration to the lymph node, and 3) Identify the difference in protein expression among two different types of breast cancer (Triple-Negative and Luminal A) and understand their aggressive biology.