A tumor derived motility factor that stimulates cell migration on extracellular matrix.
A factor that stimulates migration of lung carcinoma cells on biological substrata was purified from the human lung adenocarcinoma cell line WART. A partially purified autocrine motility factor-like substance, termed haptotaxin, was added to the lower compartment of Boyden chambers and the filters were coated on the upper, lower or both sides with different concentrations of the extracellular matrix (ECM) components fibronectin, laminin or collagen type IV. These adhesive proteins coated on the lower surface of the filter promoted the migration (haptotaxis) of lung carcinoma cells. This effect was greatly enhanced by the addition of haptotaxin. In contrast, ECM components (including gelatin) coated on the upper surface or on both filter surfaces did not stimulate tumor cell migration. However, the addition of haptotaxin also timulated cell migration under these conditions. Haptotaxin did not stimulate migration on filters coated with bovine serum albumin or on uncoated filters. Haptotaxin could not be absorbed by fibronectin, laminin, collagen type IV or gelatin, and soluble ECM components did not affect the locomotor effect of haptotaxin. Substrata coated with fibronectin, laminin and collagen type IV induced adhesion and spreading of lung carcinoma cells in a dose dependent fashion. Haptotaxin potentiated adhesion and spreading of tumor cells on these substrata but did not in itself mediate adhesion and spreading of the cells. Anti-VLA 2 antibodies inhibited migration to haptotaxin on gelatin and laminin coated filters but did not affect haptotaxin-induced migration on fibronectin or collagen type IV substrata. Anti-VLA-5 monoclonal antibodies inhibited haptotaxin-induced migration on fibronectin coated filters but not such migration on filters coated with other ECM molecules showing that tumor cells must interact specifically with ECM components in order to migrate to haptotaxin.
Klominek
J
J
Department of Lung Medicine, Karolinska Institute, Huddinge University Hospital, Sweden. Julius.Klominek@impi.ki.se
Robért
K H
KH
Sundqvist
K G
KG
D000230:Adenocarcinoma; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D005780:Gelatin / Q000494:pharmacology; D005956:Glucose-6-Phosphate Isomerase / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms; D009842:Oligopeptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000970:Antineoplastic Agents; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; C092614:glycyl-arginyl-glycyl-glutamyl-serine; C113529:haptotaxin; D005780:Gelatin; D003094:Collagen; C049554:glycyl-arginyl-glycyl-aspartyl-serine; D005956:Glucose-6-Phosphate Isomerase