Research Expertise:
Cancer Biology | Tumor Progression | Metastasis | Intravasation

My research focuses predominantly on the molecular mechanisms of intravasation, the rate-limiting step of metastasis, and resistance/susceptibility of lymphovascular emboli to therapeutics.

Metastasis poses the single most difficult clinical challenge in the attempt to manage and treat cancer. In this effort, I have established patient-derived xenografts, signifcantly the first (and only) human transplantable inflammatory breast cancer xenograft, called MARY-X. Inflammatory breast cancer (IBC) is one of the most aggressive types of breast cancer; nearly 100% of all women with IBC have lymph node involvement and 25% have distant metastases upon diagnosis. The signature phenotype of IBC is florid lymphovascular invasion of cancer emboli. Whereas most human xenografts grow as a subcutaneous confluent cellular mass, MARY-X grows exclusively in the murine lymphatic and blood vessels, recapitulating the phenotype displayed in human IBC and in essence providing both a preclinical IBC model and a relevant model of metastasis. MARY-X, in vitro, is a primary cellular derivative from tumor explants. These tumor cells spontaneously form tight, compact aggregates of cells termed “MARY-X spheroids”. Comparable to human IBC emboli, a persistent, over-expression of an intact E-cadherin/α, β-catenin axis mediates the compaction of both in vitro and in vivo MARY-X spheroids and tumor emboli, respectively. The in vitro MARY-X spheroid has comparative 3-dimensional (3-D) architectural/pathophysiological features to the lymphovascular embolus. Therefore MARY-X provides a relevant 3D in vitro analysis platform for drug design and development of IBC and metastatic disease i.e. the lymphovascular embolus.

Member of:
American Association for Cancer Research