4.8 Article

Platelets guide the formation of early metastatic niches

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.1411082111

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  1. American Lebanese Syrian Associated Charities
  2. Ludwig Center for Molecular Oncology at Massachusetts Institute of Technology (MIT)
  3. Koch Institute MIT National Cancer Institute [P30-CA14051]
  4. National Cancer Institute [U54-CA126515, U54 CA163109]
  5. Howard Hughes Medical Institute

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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.

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