Integrin dependent migration of lung cancer cells to extracellular matrix components

Abstract

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.

Expression of ADAM15 in lung carcinomas

“…In contrast to the study by Koukoulis et al [26], who described a variable intense reaction for αv in SCCs and ACs similar to that of the bronchial epithelium [26] and no staining for β3 in immunohistology, we could demonstrate that variable expression in αvβ3 using reverse-transcription PCR and fluorescenceactivated cell sorter analysis in lung tumor cell lines and using immunohistology in lung carcinomas. Additionally, Bredin et al [8] revealed that two of five lung cancer cell lines express the β3 chain. Furthermore, we demonstrated that both molecules were sometimes co-localized in the same tumor cell in ADAM15 as well as in αvβ3 integrinpositive lung tumors.…”

Circulating Inflammatory Endothelial Cells Contribute to Endothelial Progenitor Cell Dysfunction in Patients with Vasculitis and Kidney Involvement

“…We further tested whether the supernatants from the VAPϩ/MICAϩ cell cultures from patients with WG and healthy control subjects had the ability to induce neutrophil migration using a 48-well Boyden chamber (Neuro Probe, Gaithersburg, MD). Neutrophils were isolated from 10 normal individuals, and the assay was performed as described earlier (27,28). Migrated cells were counted in four randomly chosen microscope fields (ϫ40) in a blinded manner, and the average was determined.…”

Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

“…CD9 associates with b1 integrins but not with N-CAM SCLC reportedly expresses adhesion proteins, b1 integrins and N-CAM, and both of these molecules are likely to regulate motility and metastasis of SCLC (Scheidegger et al, 1994;Bredin et al, 1998). To explore the mechanisms involved in the reduction of OS3-R5-pZCD9 motility, coimmunoprecipitation experiments using MoAbs against these molecules were performed (Figure 4b,left panel).…”