Effect of different platelet agonists on intracellular free Ca++ concentrations in human tumor cells: possible role in tumor growth.
Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, including the interactions of tumors with the hemostatic system. We have investigated the pro-aggregating and pro-coagulant activities of human tumor cell lines cultured in vitro and the ability of different platelet agonists to induce Ca++ transients in these cells. Cells of a malignant mesothelioma line activated platelets by a thrombin-dependent mechanism; on the contrary, HeLa cells, derived from a uterine cervical cancer, possessed ADP-dependent pro-aggregating activity, and DND-IA melanoma cells did not stimulate platelet aggregation. All cell lines showed a tissue-factor-like procoagulant property, more pronounced in mesothelioma cells. Furthermore, ADP was able to induce a transient increase in cytoplasmic Ca++ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines investigated. Finally, the calcium-channel blocker verapamil inhibited agonist-induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data may help to identify new possible mechanisms of the 2-way interaction of tumors with the hemostatic system.
Saporiti
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A
Department of Internal Medicine, University of Pavia, IRCCS Policlinico S. Matteo, Italy.
Brocchieri
A
A
Porta
C
C
Moroni
M
M
Grignani
G
G
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D007975:Leukotriene B4; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D014700:Verapamil; D013917:Thrombin; D002118:Calcium