Integrin dependent migration of lung cancer cells to extracellular matrix components.
Since tumour progression is dependent on the ability of malignant cells to interact with the extracellular matrix (ECM), we have investigated the significance of beta1 and beta3 integrins for migration of lung cancer cells to components of the ECM. In an in vitro hapto- and chemotactic assay system, five cell lines representing the major types of lung cancer were examined: adenocarcinoma (WART); squamous cell carcinoma (U-1752); small cell lung cancer (SCLC) (U-1906, 054 A) and large cell lung cancer (LCLC) (U-1810). Flow cytometric analyses were performed to characterize their integrin expression. U-1906, 054 A, WART and U-1752 all expressed beta1 integrins whereas U-1810 did not. However, U-1810 and U-1752 expressed beta3 integrins. All cell lines except U-1810 and U-1752 showed hapto- and chemotactic motility to fibronectin, laminin and type IV collagen and this motility was beta1 integrin-dependent except in the case of U-1810. However, the hapto- and chemotactic responses differed markedly between the separate cell lines and there was no distinct pattern to separate non-small cell lung cancer (NSCLC) from SCLC. No or very little migration was seen in control experiments with bovine serum albumin (BSA) or serum-free medium alone, indicating that the migration of the lung cancer cells require adhesion molecules, soluble or substratum bound. We have found the involvement of beta1 integrins in lung cancer cell migration in vitro towards fibronectin, laminin and type IV collagen except in the case of U-1810. The U-1810 cell line clearly differed from the rest of the cell lines by lacking expression of beta1 integrins.
Bredin
C G
CG
Dept of Lung Medicine, Karolinska Institute at Huddinge University Hospital, Sweden.
Sundqvist
K G
KG
Hauzenberger
D
D
Klominek
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016023:Integrins; D009842:Oligopeptides; C049554:glycyl-arginyl-glycyl-aspartyl-serine