Platelets and cancer metastasis: a causal relationship?
Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells undergo extensive interactions with various host cells before they establish a secondary metastatic colony. Ample morphological studies have documented the close association of circulating tumor cells with host platelets. Several lines of evidence provide strong support for the concept that tumor cell-platelet interactions (i.e., TCIPA) significantly contribute to hematogenous metastasis. Clinically, cancer patients with advanced diseases are characterized by a variety of thromboembolic disorders including thrombocytosis. Pharmacologically, various anti-platelet agents/anticoagulants have demonstrated potent inhibitory effects on tumor cell-platelet interactions as well as spontaneous or experimental metastasis. Experimentally, interference with many of the intermediate steps of tumor cell-platelet interactions has resulted in diminished platelet aggregation induced by tumor cells and blocked cancer metastasis. Platelet interaction with tumor cells is a sequential process which involves two general types of mediators, i.e., membrane-bound molecules (adhesion molecules) and soluble release products. alpha IIb beta 3 integrin receptors present on both platelets as well as on tumor cells and 12(S)-HETE, a 12-lipoxygenase metabolite of arachidonic acid, are prototypical examples of each category. Mechanistically, platelets may contribute to metastasis by: (1) stabilizing tumor cell arrest in the vasculature, (2) stimulating tumor cell proliferation, (3) promoting tumor cells extravasation by potentiating tumor cell-induced endothelial cell retraction, and (4) enhancing tumor cell interaction with the extracellular matrix.
Honn
K V
KV
Department of Radiation Oncology, Wayne State University, Detroit, MI 48202.
Tang
D G
DG
Crissman
J D
JD
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D010974:Platelet Aggregation / Q000502:physiology