Platelet and Shear Rate Promote Tumor Cell Adhesion to Human Endothelial Extracellular Matrix - Absence of a Role for Platelet Cyclooxygenase

Summary

Blood platelets are thought to be involved in certain aspects of malignant dissemination. To study the role of platelets in tumor cell adherence to vascular endothelium we performed studies under static and flow conditions, measuring tumor cell adhesion in the absence or presence of platelets. We used highly metastatic human adenocarcinoma cells of the lung, cultured human umbilical vein endothelial cells (ECs) and extracellular matrices (ECM) prepared from confluent EC monolayers. Our results indicated that under static conditions platelets do not significantly increase tumor cell adhesion to either intact ECs or to exposed ECM. Conversely, the studies performed under flow conditions using the flat chamber perfusion system indicated that the presence of 2 × 10⁵ pl/μl in the perfusate significantly increased the number of tumor cells adhered to ECM, and that this effect was shear rate dependent. The maximal values of tumor cell adhesion were obtained, in presence of platelets, at a shear rate of 1,300 sec^-1. Furthermore, our results with ASA-treated platelets suggest that the role of platelets in enhancing tumor cell adhesion to ECM is independent of the activation of the platelet cyclooxygenase pathway.

Keywords

Tumor cell - Platelet - Endothelial cell adhesion

• References

• 1 Rickies FR, Edwards RL. Activation of blood coagulation in cancer. Trousseau’s syndrome revisited Blood 1983; 62: 14-28
• 2 Jamieson GA, Bastida E, Ordinas A. Interaction of platelets and tumor cells. In: Platelets in Biology and Pathology III. Chapter 5. MacIntyre DE, Gordon JL. eds Elsevier; Amsterdam: 1987. pp 161-190
• 3 Gasic G, Gasic T, Stewart CC. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci 1968; 61: 46-52
• 4 Pearlstein E, Cooper LB, Karpatkin S. Extraction and characterization of a platelet aggregating material from SV40-transformed mouse fibroblasts. J Lab Clin Med 1979; 93 (02) 332-334
• 5 Bastida E, Ordinas A, Jamieson GA. Differing platelet aggregating effects by two human cell lines. Absence of role for platelet derived ADP Am J Hematol 1981; 11: 367-378
• 6 Bastida E, Ordinas A, Escolar G, Jamieson GA. Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation and thrombogenesis. Blood 1984; 64: 177-184
• 7 Honn KV, Busse WD, Sloane BR. Prostacyclin and thromboxanes. Implications for their role in tumor cell metastasis Biochem Pharmacol 1983; 1: 1-11
• 8 Turitto VT, Baumgartner HR. Platelet-surface interactions. In: Haemostasis and Thrombosis. Colman RW, Hirsh J, Marder VJ, Salzman E. eds JB Lippincott Company; Philadelphia, PA: 1982. p 364
• 9 Nicolson GL. Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 1982; 30: 214-220
• 10 Sloane BF, Cavanaugh PG, Honn KV. Tumor cysteine proteinases, platelet aggregation and metastasis. In: Hemostatic Mechanisms and Metastasis. Honn KV, Sloane BF. eds Martinus Nijhoff; The Hague: 1984. pp 170-191
• 11 Thakur ML, Welch MJ, Joist JH, Coleman RE. Indium-111-labeled platelets: Studies on preparation and evaluation of “in vitro” and “in vivo” function. Thromb Res 1976; 9: 345-357
• 12 Jaffe EA, Nachman RL, Becker AG, Minick CR. Culture of human endothelial cells derived from umbilical veins. J Clin Invest 1973; 52: 2745-2746
• 13 De Groot PG, Reinders JH, Sixma JJ. Perturbation of human endothelial cells by thrombin or PMA changes the reactivity of their extracellular matrix towards platelets. J Cell Biol 1987; 104: 697-704
• 14 Bastida E, Escolar G, Ordinas A, Giardina SL, Jamieson GA. Effects of divalent cations on the interaction of platelets with tumor cells: aggregation and perfusion studies with two homologous human systems. J Lab Clin Med 1985; 106: 68-74
• 15 Castillo R, Lozano T, Escolar G, Revert L, López J, Ordinas A. Defective platelet adhesion on vessel subendothelium in uremic patients. Blood 1986; 62: 337-342
• 16 Sakariassen KS, Aarts PA M M, de Groot PhG, Houdijk PM, Sixma JJ. A perfusion chamber developed to investigate the interaction of flowing blood with human vessel wall cells, their extracellular matrix, and purified components. J Lab Clin Med 1983; 102: 522-535
• 17 Nicholson GL, Irimura T, Nakajima M, Updyke TV, Poste G. The cellular interactions of metastatic tumor cells with special reference to endothelial cells and their basal lamina-like matrix. In: Hemostatic Mechanisms and Metastases. Chapter 4. Honn KV, Sloane BF. eds Martinus Nijhoff; The Hague. 1984. pp 295-318
• 18 Gasic G, Gasic T. Removal of sialic acid from the cell coat in tumor cells and vascular endothelium and its effects on metastasis. Proc Natl Acad Sci 1962; 67: 793-798
• 19 Holme R, Oftebro R, Hovig T. In vitro interaction between cultured cells and human blood platelets. Thromb Haemostas 1978; 40: 89-102
• 20 Cavanaugh PG, Sloane BF, Bajkonsij AS, Gasic GJ, Gasic TB, Honn KV. Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clin Exp Metastasis 1983; 1 (04) 297-307
• 21 Bastida E, Ordinas A. Platelet contribution to the formation of metastatic Foci: The role of cancer cell-induced platelet activation. Haemostasis 1988; 18: 29-36
• 22 Bastida E, Ordinas A, Jamieson GA. Idiosyncratic platelet responses to human tumour cells. Nature 1981; (291) 5817: 661-662
• 23 Warren BA. Evidence of the blood borne tumor embolus adherent to vessel wall. J Med 1973; 6: 150-177
• 24 Bastida E, Ordinas A, Jamieson GA. Differing platelet aggregating effects by two tumor cell lines: absence of role for platelet-derived ADP. Am J Hematol 1981; 11: 367-378
• 25 Abecassis J, Millon-Collard R, Klein-Soyer C, Nicora F, Flicker JP, Beretz A, Eber R, Muller D, Cazenave JP. Adhesion of a human brest cancer cell line MCF-7 to human vascular endothelial cells in culture. Enhancement by activated platelets Int J Cancer 1987; 40: 525-531
• 26 Bastida E, Almirall L, Ordinas A. Tumor cell-induced platelet aggregation is a glycoprotein dependent and lipooxygenase mediated process. Int J Cancer 1987; 39: 760-763