Platelet aggregating material (PAM) of two virally-transformed tumors: SV3T3 mouse fibroblast and PW20 rat renal sarcoma. Role of cell surface sialylation.
Platelets are required for certain experimental tumor metastases and several lines of tumor cells have been shown to aggregate platelets. We have extracted a sedimentable sialolipoprotein, platelet aggregating material (PAM) from the cell surface of SV40 transformed Balb C3T3 fibroblasts which aggregates heparinized PRP at 2.5 micrograms/ml via the release reaction, following a one minute lag period. A similar extract from non-transformed 3T3 cells has barely measurable activity at 40 micrograms/ml. Gel-filtered platelets (GFP) do not aggregate with PAM. However, PAM aggregation can be restored by addition of 5% plasma but not by fibrinogen. Two plasma components are required: a heat-labile complement component which is activated during the lag period; and a heat-stable factor which is required for platelet aggregation. The pathophysiologic significance of PAM has been examined in ten variant cell lines derived from a spontaneously metastatic renal cell sarcoma of rats, initially induced with polyoma virus (PW20 Wistar-Furth parental lines). These lines were selected in vitro and in vivo from a single line and differed in their capacity to form distant tumors in various organs after subcutaneous injection. These cells were examined for cell surface sialylation, PAM and PAM sialic acid content, since cell surface sialic acid is increased in a variety of tumor tissues and PAM is inhibited by neuraminidase. A good correlation was obtained between in vivo metastatic potential and cell surface sialic acid, r = 0.83, p less than 0.003; cell surface sialic acid and PAM, r = 0.85, p less than 0.002; in vivo metastatic potential and sialic acid content of PAM, r = 0.69, p less than 0.03; and in vivo metastatic potential and PAM, r = 0.68, p less than 0.03. We conclude that platelets may play a role in hematogenous metastasis via the ability of tumor cells to aggregate platelets by cell surface constituents containing sialic acid. The platelet-tumor cell interaction requires activation of the alternate complement pathway and a heat stable plasma factor.
D000818:Animals; D001779:Blood Coagulation Factors / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006801:Humans; D007680:Kidney Neoplasms / Q000503:physiopathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D012513:Sarcoma, Experimental / Q000503:physiopathology*; D012794:Sialic Acids / Q000502:physiology*; D014508:Urea / Q000494:pharmacology
D001779:Blood Coagulation Factors; D010972:Platelet Activating Factor; D012794:Sialic Acids; D014508:Urea