Stephen J. Weiss, MD

Validating new therapeutic targets to prevent metastatic breast cancer.

Impact

Aggressive breast cancers arise as a result of tumor cells’ ability to invade local tissues, gain access to blood or lymphatic vessels, and exit at distant sites where the cells grow anew—a process called metastasis. Dr. Weiss is studying a sub-population of breast cancer cells, termed cancer stem cells, that play a critical role in metastasis. The evolution of breast cancer stem cells has remained unclear, and this has thwarted the development of new therapeutic interventions. Identifying important players in cancer stem cell growth and survival could provide important insights for the development of new therapeutic interventions for breast cancer patients.

Progress Thus Far

Dr. Weiss and his team have discovered a role for a breast cancer-associated gene called MT1-MMP in driving breast cancer’s ability to build new blood vessels and metastasize. The team discovered that cancer cells use MT1-MPP to cut away collagen—a structural protein that makes up the bulk of tissue—and hollow out space in tissue for tumors to expand and grow. Surprisingly, they found that cut collagen can provide an energy source to cancer cells when their access to key nutrients is limited. The team also found that this gene is expressed in blood vessels and lymph nodes near growing tumors. They found that lymph node cells use MT1-MMP to control their normal function when breast cancer cells move into surrounding lymph nodes. Moreover, inhibiting MT1-MMP activity controls both the ability of metastatic cells to proliferate as well as the ability of breast cancer cells to thwart immune system responsiveness.

What’s next

Over the next year, Dr. Weiss and his team will continue to study how MT1-MMP fuels breast cancer growth, which is especially relevant as they have observed MT1-MMP in breast cancer biopsies. The team is also focusing on studies designed to identify how cells use MT1-MMP to support metastatic growth, which could reveal therapeutic targets. Finally, they also seek to define how a specialized lymph node cell, called a fibroblast reticular cell, uses MT1-MMP to support normal immune cell function when tumors reach lymph nodes.