scholarly journals RET-Mediated Cell Adhesion and Migration Require Multiple Integrin Subunits

2010 ◽  
Vol 95 (11) ◽  
pp. E342-E346 ◽  
Author(s):  
Jessica G. Cockburn ◽  
Douglas S. Richardson ◽  
Taranjit S. Gujral ◽  
Lois M. Mulligan

Context: The RET receptor tyrosine kinase is an important mediator of several human diseases, most notably of neuroendocrine cancers. These diseases are characterized by aberrant cell migration, a process tightly regulated by integrins. Objective: Our goals were to investigate the role of integrins in RET-mediated migration in two neoplastic cell models: the neural-derived cell line SH-SY5Y, and the papillary thyroid carcinoma cell line TPC-1. We also evaluated whether multiple integrin subunits have a role in RET-mediated cell migration. Design: We evaluated the expression and activation of integrins in response to RET activation using standard cell adhesion and migration (wound-healing) assays. We examined focal adhesion formation, using integrin-paxillin coimmunoprecipitations and immunofluorescence, as an indicator of integrin activity. Results: Our data indicate that β1 integrin (ITGB1) is expressed in both SH-SY5Y and TPC-1 cell lines and that these cells adhere strongly to matrices preferentially associated with ITGB1. We showed that RET can activate ITGB1, and that RET-induced cell adhesion and migration require ITGB1. Furthermore, we showed that β3 integrin (ITGB3) also plays a role in RET-mediated cell adhesion and migration in vitro and ITGB3 expression correlates with RET-mediated invasion in a mouse tumor xenograft model, suggesting that RET mediates the activity of multiple integrin subunits. Conclusions: Our data are the first to show that multiple integrin subunits contribute to cell adhesion and migration downstream of RET, suggesting that coordinated signaling through these pathways is important for cell interactions with the microenvironment during tumor invasion and progression.

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2687-2702 ◽  
Author(s):  
M. Delannet ◽  
F. Martin ◽  
B. Bossy ◽  
D.A. Cheresh ◽  
L.F. Reichardt ◽  
...  

To identify potentially important extracellular matrix adhesive molecules in neural crest cell migration, the possible role of vitronectin and its corresponding integrin receptors was examined in the adhesion and migration of avian neural crest cells in vitro. Adhesion and migration on vitronectin were comparable to those found on fibronectin and could be almost entirely abolished by antibodies against vitronectin and by RGD peptides. Immunoprecipitation and immunocytochemistry analyses revealed that neural crest cells expressed primarily the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins as possible vitronectin receptors. Inhibition assays of cellular adhesion and migration with function-perturbing antibodies demonstrated that adhesion of neural crest cells to vitronectin was mediated essentially by one or more of the different alpha V integrins, with a possible preeminence of alpha V beta 1, whereas cell migration involved mostly the alpha V beta 3 and alpha V beta 5 integrins. Immunofluorescence labeling of cultured motile neural crest cells revealed that the alpha V integrins are differentially distributed on the cell surface. The beta 1 and alpha V subunits were both diffuse on the surface of cells and in focal adhesion sites in association with vinculin, talin and alpha-actinin, whereas the alpha V beta 3 and alpha V beta 5 integrins were essentially diffuse on the cell surface. Finally, vitronectin could be detected by immunoblotting and immunohistochemistry in the early embryo during the ontogeny of the neural crest. It was in particular closely associated with the surface of migrating neural crest cells. In conclusion, our study indicates that neural crest cells can adhere to and migrate on vitronectin in vitro by an RGD-dependent mechanism involving at least the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins and that these integrins may have specific roles in the control of cell adhesion and migration.


2019 ◽  
Vol 72 (3) ◽  
pp. 528-537 ◽  
Author(s):  
Jens Mani ◽  
Jens Neuschäfer ◽  
Christian Resch ◽  
Jochen Rutz ◽  
Sebastian Maxeiner ◽  
...  

1983 ◽  
Vol 96 (2) ◽  
pp. 462-473 ◽  
Author(s):  
R A Rovasio ◽  
A Delouvee ◽  
K M Yamada ◽  
R Timpl ◽  
J P Thiery

Cells of the neural crest participate in a major class of cell migratory events during embryonic development. From indirect evidence, it has been suggested that fibronectin (FN) might be involved in these events. We have directly tested the role of FN in neural crest cell adhesion and migration using several in vitro model systems. Avian trunk neural crest cells adhered readily to purified plasma FN substrates and to extracellular matrices containing cellular FN. Their adhesion was inhibited by antibodies to a cell-binding fragment of FN. In contrast, these cells did not adhere to glass, type I collagen, or to bovine serum albumin in the absence of FN. Neural crest cell adhesion to laminin (LN) was significantly less than to FN; however, culturing of crest cells under conditions producing an epithelioid phenotype resulted in cells that could bind equally as well to LN as to FN. The migration of neural crest cells appeared to depend on both the substrate and the extent of cell interactions. Cells migrated substantially more rapidly on FN than on LN or type I collagen substrates; if provided a choice between stripes of FN and glass or LN, cells migrated preferentially on the FN. Migration was inhibited by antibodies against the cell-binding region of FN, and the inhibition could be reversed by a subsequent addition of exogenous FN. However, the migration on FN was random and displayed little persistence of direction unless cells were at high densities that permitted frequent contacts. The in vitro rate of migration of cells on FN-containing matrices was 50 microns/h, similar to their migration rates along the narrow regions of FN-containing extracellular matrix in migratory pathways in vivo. These results indicate that FN is important for neural crest cell adhesion and migration and that the high cell densities of neural crest cells in the transient, narrow migratory pathways found in the embryo are necessary for effective directional migration.


2002 ◽  
Vol 20 (3) ◽  
pp. 285-304 ◽  
Author(s):  
Paola Spessotto ◽  
Emiliana Giacomello ◽  
Roberto Perris

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257495
Author(s):  
Janine Riegert ◽  
Alexander Töpel ◽  
Jana Schieren ◽  
Renee Coryn ◽  
Stella Dibenedetto ◽  
...  

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.


Author(s):  
Paola Spessotto ◽  
Katia Lacrima ◽  
Pier Andrea Nicolosi ◽  
Eliana Pivetta ◽  
Martina Scapolan ◽  
...  

Author(s):  
Leila Mohammadi ◽  
Bashir Mosayyebi ◽  
Mahsa Imani ◽  
Mohammad Rahmati

Background: Aberrant expression of cell adhesion molecules and matrix metalloproteinase (MMPs) plays a pivotal role in tumor biological processes including progression and metastasis of cancer cells. Targeting these processes and detailed understanding of their underlying molecular mechanism is an essential step in cancer treatment. Dexamethasone (Dex) is a type of synthetic corticosteroid hormone used as adjuvant therapy in combination with current cancer treatments such as chemotherapy in order to alleviate its side effects like acute nausea and vomiting. Recent evidences have suggested that Dex may have antitumor characteristics. Objective: Dex affects the migration and adhesion of T47D breast cancer cells as well as cell adhesion molecules e.g., cadherin and integrin, and MMPs by regulating the expression levels of associated genes. Methods: In this study, we evaluated the cytotoxicity of Dex on the T47D breast cancer cell line through MTT assay. Cell adhesion assay and wound healing assay were performed to determine the impact of Dex on cell adhesion and cell migration, respectively. Moreover, real-time PCR was used to measure the levels of α and β integrin, E-cadherin, N-cadherin, MMP-2, and MMP-9. Results: Dex decreased the viability of T47D cells in a time and dose-dependent manner. Cell adhesion and migration of T47D cells were reduced upon Dex treatment. The expression of α and β integrin, E-cadherin, N-cadherin, MMP-2, and MMP-9 were altered in response to the Dex treatment. Conclusion: Our findings demonstrated that Dex may have a role in the prevention of metastasis in this cell line.


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