Member, Department of Cell Biology and Biology
Memorial Sloan Kettering Cancer Center
New York, New York
Dr. Benezra has previously shown that neutrophils (a type of white blood cell involved in innate immunity) exhibit anti-metastatic properties when stimulated by the primary tumor in laboratory models of breast cancer. Furthermore, his team has shown that neutrophils isolated from human breast cancer patients are capable of killing breast cancer cells. Their recent data has shown that serum levels of three cytokines (cell signaling proteins), IL1A, MCP-1 and TNFα, are associated with the cancer cell killing capacity of neutrophils isolated from human patients. Moreover, stimulation of neutrophils with these cytokines results in cancer cell death in vitro. Further analyses of these signaling proteins and the molecular pathways that they activate may identify a means to stimulate the cancer cell killing capacity of neutrophils in breast cancer patients, and ultimately lead to a decrease in the incidence of metastatic progression.
Dr. Benezra’s laboratory has previously shown that neutrophils (a component of the immune system), stimulated by the primary tumor, have anti-metastatic properties and the capacity to kill tumor cells in laboratory models of breast cancer. However others have reported pro-metastatic properties of neutrophils. To further investigate the role of neutrophils in metastasis, and whether their phenotypes change with disease progression, the Benezra team has characterized various properties of neutrophils isolated from mice at early and late time points during tumor development. They have previously shown that these two neutrophil groups differ in the expression of certain signaling molecules and have now further characterized these early and late neutrophils by investigating their secretion of select cytokines and gene expression profiles. These analyses may identify targets suitable for the development of agents capable of stimulating or enhancing the anti-tumor activities of neutrophils, and lead to new therapeutics for the treatment and/or prevention of metastatic disease.
Robert Benezra, PhD, is a Member at Memorial Sloan-Kettering Cancer (MSKCC) in the Department of Cell Biology and a Professor of Biology at Cornell Graduate School of Medical Sciences in New York City. Before he joined MSKCC, Benezra worked at Fred Hutchinson Cancer Center in Seattle where he identified the Id proteins as dominant negative regulators of the helix-loop-helix protein family, and has since gone on to identify these proteins as key regulators of tumor growth, angiogenesis and metastasis.
In addition, while at MSKCC, Benezra and his colleagues identified the first human mitotic checkpoint gene, hsMad2, and demonstrated that its de-regulation leads to chromosome instability, tumor progression and drug resistance. His program continues to focus on the molecular basis of tumor angiogenesis, tumor instability and metastasis and is currently developing molecular and cellular tools to inhibit these processes in patients.