title: Platelets guide the formation of early metastatic niches.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; andDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105 rohynes@mit.edu myriam.labelle@stjude.org.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labelle
authors.affiliation: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
authors.forename: Shahinoor
authors.initials: S
authors.lastname: Begum
authors.affiliation: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; and rohynes@mit.edu myriam.labelle@stjude.org.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D045744:Cell Line, Tumor; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006098:Granulocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D054365:Chemokine CXCL5; D019743:Chemokines, CXC; C094739:Cxcl5 protein, mouse; C446301:Cxcl7 protein, mouse; D009363:Neoplasm Proteins; D023063:Receptors, Interleukin-8B