Heparin receptors in two murine mammary adenocarcinomas with different metastatic ability: relationship with growth inhibition.
Binding of heparin to primary cultured cells of two murine mammary adenocarcinomas with low (M3) and high (MM3) lung, metastatic capacity was determined. Heparin binding was rapid, specific and saturable. MM3 cells grown for 24 h in fetal calf serum (FCS)-free medium exhibited a higher number of binding sites for 3H-heparin [(11 +/- 1) x 10(5) sites per cell than M3 cells [(6.9 +/- 0.6) x 10(5) sites per cell]. However, when M3 cells were grown in the presence of 2% FCS, they showed less heparin binding sites [(3.5 +/- 0.4) x 10(5) sites per cell]. In contrast, dissociation constants were very similar for MM3 and M3 cells grown with or without FCS (Kd = 2-4 x 10(-9) M). Furthermore, heparin inhibited MM3 and M3 cell growth both in the absence or presence of FCS. Competition studies showed that chemically modified heparins lacking antiproliferative effect (O-desulfated; O/N-desulfated N-acetylated and N-desulfated heparins) were not able to inhibit 3H-heparin binding. N-desulfated N-acetylated heparin, which had partial antiproliferative effect, partially inhibited 3H-heparin binding, while heparin with a high antiproliferative activity inhibited more than 90% 3H-heparin binding. The antiproliferative effect of heparin and chemically modified heparins seems to be related to their binding ability to the cell membrane.
Esteban Bertolesi
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Area Investigación, Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Argentina.
Lauría de Cidre
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Sacerdote de Lustig
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Eiján
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D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006493:Heparin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; C037680:heparin receptor; D006493:Heparin