Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness

Palecek, Sean P.; Loftus, Joseph C.; Ginsberg, Mark H.; Lauffenburger, Douglas A.; Horwitz, Alan F.

doi:10.1038/385537a0

Cited by 1,294 publications

(1,098 citation statements)

References 28 publications

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“…In contrast to the results of adhesion and spreading assay, of all the CHO cells investigated, CHO-K1 cells with the native level of a5 migrated most effectively to fibronectin ( Figure 4C). These data are consistent with the theory that cell migration is controlled by dynamic interactions between cell receptors and substratum ligands in a manner representing events at the front and rear of the migrating cells (Palecek et al, 1996(Palecek et al, , 1997Regen and Horwitz, 1992). The rate of kidney metastasis appears to shift in parallel with the adhesion of CHO cells to fibronectin, except for a5CHO cells that do not develop a primary site.…”

Section: Adhesion and Migration Of Cho Cells To Fibronectin In Vitrosupporting

confidence: 88%

Expression level of integrin α5 on tumour cells affects the rate of metastasis to the kidney

et al. 2003

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Tumour metastasis is known clinically to have organ specificity. We hypothesised that integrins might be involved in determining the organ specificity of tumour metastasis. Here, we report the results of spontaneous metastasis tested in nude mice that were inoculated with Chinese hamster ovary (CHO) cells expressing integrin a5b1 at various levels. The growth of the primary tumour inversely correlated with the a5 expression level on CHO cells, which is consistent with a previous report (Schreiner et al, 1991). The rates of pulmonary, lymph node, and adrenal metastases that developed in nude mice were not related to changes of the a5 expression level on CHO cells. Kidney metastasis developed in 40% of nude mice inoculated with a5B2 cells (CHO cells overexpressing a5) and in 20% of mice with CHO-K1 cells (CHO cells expressing native a5), whereas inoculation with CHO-B2 cells (a5-defective mutants) and a5CHO cells with the highest expression of a5 did not lead to development of kidney metastasis. Furthermore, a5CHO, which shows the slowest growth of these cell types, did not lead to primary tumours in nude mice. These findings suggest that there is an appropriate level of a5 expression on tumour cells that leads to metastasis. Microscopic observations revealed that micrometastasis in the kidney was formed in glomeruli. An adhesion assay using frozen sections of the kidney demonstrated that a5B2 cells, but not CHO-B2 cells, effectively adhered to glomeruli. Kidney metastasis in vivo and the adhesion of a5B2 to glomeruli shown ex vivo were significantly suppressed by the administration of GRGDS peptide. Finally, we conclude that the interaction of a5b1 on tumour cells with fibronectin in kidney glomeruli is involved in kidney metastasis and that the tumour has appropriate levels of integrins crucial for metastasis.

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Section: Adhesion and Migration Of Cho Cells To Fibronectin In Vitrosupporting

confidence: 88%

Expression level of integrin α5 on tumour cells affects the rate of metastasis to the kidney

et al. 2003

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“…After this is the detachment to the substrate at the rear of the cell, allowing tail retraction and forward translocation of the cell body [20,21]. The ability to spread and subsequently migrate depends on a critical value of adhesive strength between cell and substrate: high or low levels of substrate attachment inhibit spreading and migration, whereas maximum migration occurs at intermediate adhesion strengths [22]. We found that SMC transfected by VCAM-1 siRNA displayed significant inhibition in migration compared to the cells transfected with control siRNA.…”

Section: Discussionmentioning

confidence: 99%

siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration

et al. 2008

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Vascular cell adhesion molecule-1 (VCAM-1) is an adhesion molecule expressed by endothelial cells for recruitment of leukocytes during inflammation. It is also abundantly expressed by smooth muscle cells in atherosclerotic lesions and in injured arteries. In this study, we examined the role of VCAM-1 in smooth muscle cell migration. Smooth muscle cells were isolated from the aorta of C57BL/6 mice and transfected with short interfering RNAs (siRNAs) targeting VCAM-1. Inhibition on VCAM-1 expression by siRNAs was assessed by Western blot analysis, RT-PCR and by measuring soluble VCAM-1 concentrations in the incubation medium. One siRNA that showed greater suppression on VCAM-1 expression was used for migration assay. A single scratch wound was made on 70% confluent cells and cells migrated from wounded monolayer were counted 24 and 48 h after injury. Treatment with VCAM-1 siRNA resulted in a significant reduction in the number of migrated cells. This siRNA also exhibited a minor effect on smooth muscle cell proliferation. Thus, our findings indicate that VCAM-1 is necessary for the migration of smooth muscle cells and interfering VCAM-1 expression could be an effective approach to prevention and treatment of atherosclerosis and restenosis.

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“…Studies with cultured cells have shown a close correlation between cell-substratum adhesive strength and migration rates [131]. Evidence for a role of syndecans in modulating cell-migration activity comes from studies of lymphocyte migration.…”

Section: Cell Migrationmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

618

497

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This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.

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Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness

Cited by 1,294 publications

References 28 publications

Expression level of integrin α5 on tumour cells affects the rate of metastasis to the kidney

Expression level of integrin α5 on tumour cells affects the rate of metastasis to the kidney

siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration

Syndecans: multifunctional cell-surface co-receptors

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