Effect of phosphodiesterase inhibitors on platelet aggregation and tumor metastasis.
Recent studies suggest a relationship of platelet aggregation to metastatic spread of neoplasia. In the present experiment pentoxifylline appears to be a highly effective platelet aggregation inhibitor: a dose-response curve is apparent in monkey between 6 and 24 mg/kg i.v. Besides pentoxifylline significantly reduces metastasis rates in Wilms' tumor and neuroblastoma in rodents: 18 mg/kg significantly increase polyploid Ehrlich ascites tumor cell circulation time; on the contrary it has no effect on metastasis in the NIH renal adenocarcinoma. It is thus possible that platelet factor related blood coagulation processes play a different role in the fate of these tumor cells. This may be related to cell membrane characteristics. Phosphodiesterase inhibitors alter membrane fluidity and cell deformability of cancer cells which may pass the microcirculation easier and are less likely to settle and form metastases. Agents with both platelet aggregation inhibitory and red cell deformability increasing effect may find a place in our therapeutic armamentarium in oncology.
D000230:Adenocarcinoma / Q000188:drug therapy; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000556:secondary; D008251:Macaca; D008297:Male; D051379:Mice; D009012:Mopidamol / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D010431:Pentoxifylline / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D013805:Theobromine / Q000031:analogs & derivatives*; D009396:Wilms Tumor / Q000188:drug therapy
D009012:Mopidamol; D000244:Adenosine Diphosphate; D013805:Theobromine; D010431:Pentoxifylline