What are the mechanisms that enable cancer tumor cells to spread from their original site but remain dormant for some time prior to becoming metastatic and threatening the lives of patients? That is the disseminated tumor cells that have left the primary tumor and successfully seeded secondary target organs, but have not yet formed tumors. This scenario is recognized as crucial in initiating metastasis years or decades after patients have undergone cancer treatment. And this is the main cause of death among those patients with cancer. Now the Tisch Cancer Institute at Mount Sinai received a $1.9 million grant by the National Cancer Institute (NCI) to investigate these mechanisms over the next five years. Led by Jose Javier Bravo-Cordero, PhD, the Mount Sinai team’s hypothesis points to the position that these dormant disseminated tumor cells are quite active, constructing a dormancy-supportive extracellular matrix (ECM) nice, rich in an ECM protein known as collagen III.
TrialSite provides the network a brief breakdown of this important research.
What’s Going on During Tumor Dormancy?
Metastasis—cancer that has spread from its original site to grow in other parts of the body—is the main cause of death among patients with cancer, but the mechanisms involved in this phenomenon are unclear. Disseminated tumor cells, cells that have left the primary tumor and successfully seeded secondary target organs but have not yet formed tumors, have been recognized as crucial in initiating metastasis years or decades after patients have undergone cancer treatment.
This delay in growth is mediated by a process called tumor dormancy, in which tumor cells cease dividing but can be reactivated under the right environmental conditions. These cells are less vulnerable to the immune system and cancer treatments, including chemo and radiation. Studies have shown that tumor cell interactions with the extracellular matrix (ECM)—a molecular network that contributes to the structural integrity and strength of surrounding cells—regulate the hallmarks of cancer from tumor growth to metastasis. However, the role that ECM molecules and receptors play in the dormancy of disseminated tumor cells is unknown, as is whether the tumor cells develop dormancy-supportive niches that sustain them in this state.
What is the study’s hypothesis?
As declared by Dr. Bravo-Cordero, “Our hypothesis is that the dormant disseminated tumor cells are constructing a dormancy-supportive ECM niche that is rich in collagen III, an ECM protein.”
Now with the funding the Mount Sinai team can leverage high-resolution imaging tools combined with dormancy models to investigate tumor cell-ECM interactions during dormancy. The team will develop an imaging approach that includes multiphoton imaging and second harmonic generation as well as activity reporters for dormancy-related genetic pathways.
The principal investigator mentioned, “This grant will enable us to better understand the role of collagen III in the construction of these niches at the metastatic organs and define the factors in the tumor ECM microenvironment that contribute to this phenomenon.”
Dr. Bravo-Cordero continued, “Uncovering the mechanisms that regulate dormant cell-ECM interactions will enable us to devise strategies that either prevent the awakening of the disseminated cells or that enable us to kill these cells by targeting the ECM microenvironment, which would result in a significant reduction in the annual number of deaths from metastatic cancers.”
About the Mount Sinai Health System
The Mount Sinai Health System is New York City’s largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care—from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report’s “Honor Roll” of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in the country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% or all physicians nationally by U.S. News & World Report.
Jose Javier Bravo-Cordero, PhD, Assistant Professor of Medicine (Hematology and Medical Oncology), Icahn School of Medicine at Mount Sinai, Scientific Advisor in the Advanced Bioimaging Center, The Tisch Cancer Institute, Principal Investigator