Platelets guide the formation of early metastatic niches

• Main Authors: Labelle, Myriam (Contributor), Begum, Shahinoor (Contributor), Hynes, Richard O (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Hynes, Richard O. (Contributor)
• Format: Article
• Language: English
• Published: National Academy of Sciences (U.S.), 2015-02-05T17:05:25Z.
• Subjects: Article
• Online Access: Get fulltext

During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments ("niches") that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form "early metastatic niches." Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis.
Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology
National Cancer Institute (U.S.) (Support Grant P30-CA14051)
National Cancer Institute (U.S.) (Grant U54-CA126515)
National Cancer Institute (U.S.) (Grant U54 CA163109)
Howard Hughes Medical Institute