Platelets: linking hemostasis and cancer

Abstract

Platelets are the main cellular component in blood responsible for maintaining the integrity of the cardiovascular system via hemostasis. Platelet dysfunction contributes to a wide range of obvious pathological conditions, such as bleeding or thrombosis, but normal platelet function is also linked to diseases not immediately associated with hemostasis or thrombosis, such as cancer. Since the description of Trousseau syndrome in 1865, various experimental and clinical studies have detailed the interaction of platelets with primary tumors and circulating metastatic tumor cells. Observations have suggested that platelets not only augment the growth of primary tumors via angiogenesis but endow tumor cells physical and mechanical support to evade the immune system and extravasate to secondary organs, the basis of metastatic disease. Many laboratory and animal studies have identified specific targets for antiplatelet therapy that may be advantageous as adjuncts to existing cancer treatments. In this review, we summarize important platelet properties that influence tumorigenesis, including primary tumor growth and metastasis at the molecular level. The studies provide a link between the well-studied paradigms of platelet hemostasis and tumorigenesis.

Figure 1

Interactions of platelets, coagulation, and tumor cells in tumorigenesis. Schematic diagram showing the interplay among various proteins; platelet receptors, coagulation proteins, and tumor cells interacting in the process of tumorigenesis.

Figure 2

Interaction of platelets, coagulation and tumor cells. Cartoon representation showing some of the molecules implicated for tumor cells and platelets to promote interaction and influence tumor cell growth and survival.

Figure 3

Western blot analysis of human tumor cell lines for the presence of human GP Ibα antigen. Also shown are normal mouse and human platelet lysates for representative signals. The blot was reacted with an anti-α-tubulin antibody as a positive control. Human GP Ibα antigen is observed in lysates from purified human platelets (Hu Platelets) and noticeably absent in all other samples (anti-human GPIbα monoclonal antibody, LJ-Ib10, kindly provided by Zaverio Ruggeri, The Scripps Research Institute).mBSS, mouse platelet lysate missing GPIbα; C57, normal mouse platelet lysate; Hu Platelets, human platelet lysate. All other lanes contain lysate from the indicated human tumor cell line.