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Dissecting and Targeting Latent Metastasis
Annual rept. 1 Sep 2013-31 Aug 2014
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
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Metastasis is physically and psychologically devastating, frequently incurable, and the cause of 90 of deaths from breast cancer. Invasive breast tumors release cancer cells from the outset, and thousands of these cells infiltrate distant organs before the primary tumor is diagnosed and removed. Microscopic cancer colonies that remain in a patients organs after the removal of a breast tumor constitute latent metastasis of breast cancer LMBC. These cells retain the potential to form overt metastasis for years. Targeting LMBC with new drugs offers an untapped opportunity to prevent metastasis. This research project aims at identifying the cell types, organ sites, tissue niches, metastasis genes, and signaling functions that support the survival and fitness of LMBC cells. In year 02 we made progress in isolating latent metastatic cells from breast cancer and lung cancer. We implemented transcriptional analysis of selected cancer cell populations in highly heterogeneous tumor microenvironments. We identified L1CAM as a mediator of vascular cooption by disseminated metastasis-initiating cells in different organs, and as a potential therapeutic target against metastasis. We identified connexin 43 Cx43 and protocadherin 7 PCDH7 as components of gap junctions that mediate survival and colony initiation in breast cancer cells that infiltrate the brain. We showed that gap junction modulators can be safely used as inhibitors of brain metastasis of breast cancer.
APPROVED FOR PUBLIC RELEASE