Platelet-tumor interactions

Kaipatkin, S., Pearlstein, E., Ambrogio, C. and Coller, B. S. (1988). Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J. Clin. Invest. 81, 1012-1019. 

PRP and PPP preparation. If rats or mice are used, they are anaesthetized by an i.p. injection of sodium pentobarbital (50 mg/Kg), and blood is drawn into heparin (5 units/ml final) or citrate/dextrose (final concentration 0.38% and 0.48% (wt/vol), respectively) anticoagulant from the dorsal aorta or by heart puncture, with a 22-gauge needle (the choice of heparin as anticoagulant appears to be more appropriate, because chelation of divalent cations by trisodium citrate or EDTA might affect platelet-tumor cell interaction). Blood is then diluted with an equal volume of 0.9% NaCl, and centrifuged for 7 min at 400 x g on preformed gradients of 70% Percoll containing 0.9% NaCl. The yellowish supernatant is the PPP, while PRP forms a white band between PPP and the percoll layer. Platelets in PRP are counted with a Coulter counter and diluted with PPP to a concentration of 10 /ml. PPP is a source of prothrombin, and should thus be included in the assay. 

Al-Mondhiry, H. (1984). Tumor interaction with hemostasis the rationale for the use of platelet inhibitors and anticoagulants in the treatment of cancer. Am. J. Hematol. 16, 193-202. 

Gasic, G. J., Gasic, T. B., Galanti, N., Johnson, T. and Murphy, S. (1973). Platelet-tumor cell interaction in mice the role of platelets in the spread of malignant disease. Int. J. Cancer 11, 704-718. 

Fig. 6.3 Eicosanoids and Tumor-platelet interactions in metastasis and the role of 12-HETE in tumor cell extravasation. Studies have clearly shown that hematogenous route of metastasis spread of cancer cells, involves interactions with platelets. Tumor-platelet interactions and subsequent aggregation is critically controlled by a delicate balance between the level of endothelium derived PGI2 and platelet or tumor derived TXA2. Elevated TXA2 levels in the circulation can tip the balance towards platelet aggregation and tumor metastasis to distant organs, whereas increases in PGI2 levels can block this interaction preventing spread of cancer cells. Shown in this illustration is a schematic of a blood vessel, with metastatic tumor cells interacting with platelets. Interactions of tumor cells with platelets and endothelial cells have been demonstrated to induce 12(S)-HETE production, which leads to retraction of endothelial cell layers enabling metastatic tumor cells to extravasate and set up secondary colonies of metastasis...

Gasic GJ, Gasic TB, Galanti N, Johnson T, Murphy S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of mahgnant disease. Int J Cancer. 11 (1973)... 

Interaction of tumor cells in circulation with fibrin and platelets,... 

Administration of Certain Proteases to Animals Enhances Metastasis. Administration of specific proteases to animals has been found to stimulate the production of metastasis. For example, in rabbits, administration of uPA has been found to enhance the metastasis of V2 carcinomas (K11), while in mice, exogenous uPA increased pulmonary metastasis from Lewis lung carcinomas (Tl). Also, infusion of thrombin into syngenic mice stimulated pulmonary metastasis from both colon carcinoma cells and melanoma cells (N5). This enhanced formation of metastasis in the presence of thrombin may result from increased tumor cell-platelet interaction in the presence of the protease (N5). 

Pulmonary tumors," may impair some vascular endothelial functions and alter the interaction between platelet and endothelial mediators ... 

Malignant tumor cells in the blood stream interaction with blood elements and platelet aggregation... 

Interactions between tumor cells and platelets can be analyzed by different methods. The ability of tumor cells to induce platelet aggregation ( tumor cells induced platelet aggregation TCIPA) is evaluated by the turbidometric assay (Menter et al., 1987 Watanabe et al., 1988 Sugimoto et al., 1991 Tang et al., 1993 Belloc et al., 1995). Besides, the ability of tumor cells to bind platelets can be evaluated by the classic adhesion assay (see below). 

Sepsis involves activation of inflammatory pathways, and a complex interaction between proinflammatory and anti-inflammatory mediators plays a major role in the pathogenesis of sepsis. The key proinflammatory mediators include tumor necrosis factor-a (TNF-a), interleukin 1/3 (IL-1/3), and interleukin 6 (IL-6), which are released by activated macrophages. Other mediators that may be important for the pathogenesis of sepsis include interleukin 8 (IL-8), platelet-activating factor (PAF), leukotrienes, and thromboxane A2. " The significant anti-inflammatory mediators include IL-1 receptor antagonist (IL-lra), IL-4, and IL-10. These anti-inflammatory cytokines inhibit the production of the proinflammatory cytokines and down-regulate some inflammatory cells. 

K22. Kohase, M., May, L. T., Tamm, 1., Vilcek, J., and Sehgal, P. B. A cytokine network in human diploid fibroblasts Interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol. Cell. Biol. 7, 273-280 (1987). 

Rl. Rabinovici, R., Yue, T. L., Farhat, M., Smith, E. F., Esser, K. M., Slivjak, M., and Feuerstein, G. Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock Studies with BN 50739, a novel PAF antagonist. X Pharmacol Exp. Then 255, 256-263 (1990). 

The involvement of platelets in assisting hematogenous spread of metastatic tumor cells and the interactions between platelets, cancer cells, and the blood vessel wall were proposed decades ago. This was confirmed in experimental model systems of thrombocytopenia which showed inhibition of metastasis (Gasic et al., 1973 Kimoto et al., 1993). Honn et al, proposed the first hypothesis on the involvement of bioactive lipid mediators, specifically TXA2... 

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