Blood Journal
Leading the way in experimental and clinical research in hematology

A novel and essential role for FcγRIIa in cancer cell–induced platelet activation

  1. Annachiara Mitrugno1,
  2. David Williams2,
  3. Steven W. Kerrigan1, and
  4. Niamh Moran1
  1. 1Molecular and Cellular Therapeutics Department and
  2. 2Department of Geriatric and Stroke Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland

Key Points

  • The immune receptor FcγRIIa is a key mediator of tumor cell activation of platelets in the circulation.

  • Secretion of adenosine 5′-diphosphate from dense granules is the primary response of platelets to activation by tumor cells.

Abstract

Platelets play a role in cancer by acting as a dynamic reservoir of effectors that facilitate tumor vascularization, growth, and metastasis. However, little information is available about the mechanism of tumor cell–induced platelet secretion (TCIPS) or the molecular machinery by which effector molecules are released from platelets. Here we demonstrate that tumor cells directly induce platelet secretion. Preincubation of platelets with human colon cancer (Caco-2), prostate cancer (PC3M-luc), or breast cancer cells (MDA-MB-231;MCF-7) resulted in a marked dose-dependent secretion of dense granules. Importantly, TCIPS preceded aggregation which always displayed a characteristic lag time. We investigated the role of platelet receptors and downstream molecules in TCIPS. The most potent modulators of TCIPS were the pharmacologic antagonists of Syk kinase, phospholipase C and protein kinase C, all downstream mediators of the immunoreceptor tyrosine-based activation motif (ITAM) cascade in platelets. Supporting this, we demonstrated a central role for the immune Fcγ receptor IIa (FcγRIIa) in mediating platelet-tumor cell cross-talk. In conclusion, we demonstrate that cancer cells can promote platelet dense-granule secretion, which is required to augment platelet aggregation. In addition, we show a novel essential role for FcγRIIa in prostate cancer cell–induced platelet activation opening the opportunity to develop novel antimetastatic therapies.

  • Submitted March 26, 2013.
  • Accepted September 20, 2013.
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