21:T531,Selectins are adhesion receptors that normally recognize certain vascular mucin-type glycoproteins bearing the carbohydrate structure sialyl-Lewisx. The clinical prognosis and metastatic progression of many epithelial carcinomas has been correlated independently with production of tumor mucins and with enhanced expression of sialyl-Lewisx. Metastasis is thought to involve the formation of tumor-platelet-leukocyte emboli and their interactions with the endothelium of distant organs. We provide a link between these observations by showing that P-selectin, which normally binds leukocyte ligands, can promote tumor growth and facilitate the metastatic seeding of a mucin-producing carcinoma. P-selectin-deficient mice showed significantly slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases from intravenously injected cells. Three potential pathophysiological mechanisms are demonstrated: first, intravenously injected tumor cells home to the lungs of P-selectin deficient mice at a lower rate; second, P-selectin-deficient mouse platelets fail to adhere to tumor cell-surface mucins; and third, tumor cells lodged in lung vasculature after intravenous injection often are decorated with platelet clumps, and these are markedly diminished in P-selectin-deficient animals.22:T448,One hundred years have passed since Trousseau first made the observation that thrombosis may be found in association with cancer.¹Episodes of embolism²and thrombophlebitis,^3-5may precede clinical evidence of certain tumors, and nonbacterial thrombotic endocarditis is sometimes associated with neoplastic disease.⁶The thrombophlebitis seen in patients with cancer is characterized as recurrent and migrating^7,8with involvement of multiple sites, including the upper trunk and arms.^4,7,9Anticoagulation is usually ineffective in its control.^3,4Tumors of the lung, ovary, stomach, and pancreas are believed to be most commonly associated with a thrombotic tendency.^4-10 The incidence of thrombophlebitis in patients with malignant disease is low,^11,12and contributory factors often play a role in increasing the susceptibility of the cancer patient to the development of thromboses.¹²Conversely, only 3% to 5% of patients with evidence of thrombosis had cancer.^5,13 Since it is

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