Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Abstract

Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed α2 (63.8 ± 11.3% positive cells), α3 (93.3 ± 7.0%), α5 (50.4 ± 12.0%) and α6 (34.1 ± 4.9%) integrins but not α1, α4, αv or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0%) and fibronectin (40.0 ± 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that α2, α3 and α6 mediated laminin-1 adhesion, but neither α3 nor α5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5%) while simultaneously reducing α5 (24.2 ± 19%) and α6 (14.3 ± 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, α3 and α5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells), was blocked by an antibody against α6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/ migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

Free Exchange across Cells, and Echistatin-Sensitive Membrane Target for the Metastasis Inhibitor NAMI-A (Imidazoliumtrans-Imidazole Dimethyl Sulfoxide Tetrachlororuthenate) on KB Tumor Cells

“…One such target is the whole metastatic process that involves an intricate interplay between cell adhesion, proteolysis, migration, and angiogenesis (Bashyam, 2002). In this context, numerous studies have shown that modification of cell adhesive ability is strictly correlated to metastatic processes (Klominek et al, 1997;Kim et al, 2003), since the increase of this property can decrease cell metastatic capability (Roela et al, 2003).…”

The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

“…The tumor-promoting role of CD151 may also be carried out through regulation of α3β1 integrin-dependent cell-ECM adhesion, migration, survival, and signaling [ 50 , 110 , 111 , 112 ]. Such impact, however, seems largely restricted to tumor cells with basal cell lineage or a mesenchymal phenotype [ 28 , 71 , 113 ].…”

Integrins: A Method of Early Intervention in the Treatment of Colorectal Liver Metastases

“…Roela [49] 1 Colorectal cancer cell growth arrest was induced using DMSO. This was found to alter integrin expression and function -affecting tumour cell adhesion and migration.…”