The α3β1 Integrin Is Involved in Melanoma Cell Migration and Invasion

Melchiori, A; Mortarini, Roberta; Carlone, Sebastiano; Marchisio, Pier Carlo; Anichini, Andrea; Noonan, Douglas M.; Albini, Adriana

doi:10.1006/excr.1995.1223

Cited by 118 publications

(78 citation statements)

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“…Furthermore, in melanoma cells the same antibody also inhibits cell migration and invasion, and in immortalized keratinocytes a deficiency of ␣3␤1 integrin suppresses MMP-9 expression. (DiPersio et al, 2000;Melchiori et al, 1995). The novelty here is that ␣3␤1 integrin was involved in MMP-2 activation.…”

Section: Giannelli Et Almentioning

confidence: 76%

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

Giannelli

Bergamini

Fransvea

et al. 2001

Laboratory Investigation

133

134

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SUMMARY:Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver; prognosis depends on the tendency to metastasize. Cancer cell invasion is regulated by proteolytic remodeling of extracellular matrix components and by integrin expression. We have shown that matrix metalloproteinase-2 (MMP-2) and membrane-type-1 matrix metalloproteinase (MT1-MMP) cleave Laminin-5 (Ln-5), stimulating cell migration. Here we report that all HCC cells express MT1-MMP, migrate on Ln-1 and Collagen IV, whereas only HCC cells that express ␣3␤1 integrin secrete detectable levels of gelatinases, migrate on Ln-5, and invade through a reconstituted basement membrane (BM). Migration on Ln-5 is blocked by BB-94, an MMP inhibitor, and by MIG1, a monoclonal antibody that hinders migration on MMP-2-cleaved Ln-5. Invasion through a reconstituted BM is also inhibited by BB-94. HCC ␣3␤1-negative cells migrate on Ln-1 and Collagen IV, but not on Ln-5, and do not invade through a reconstituted BM, although they express MT1-MMP. Anti-␣3␤1 blocking antibodies inhibit gelatinase activation, cell motility, and cell invasion through Matrigel. In vivo, ␣3␤1 integrin and Ln-5 are expressed in HCC tissue but not in normal liver. In conclusion, our data suggest that both ␣3␤1 integrin and gelatinase activity are required for HCC migration and invasion. (Lab Invest 2001, 81:613-627).

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Section: Giannelli Et Almentioning

confidence: 76%

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

Giannelli

Bergamini

Fransvea

et al. 2001

Laboratory Investigation

133

134

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“…For example, the human melanoma cell BLM migrates over laminin and expresses ␣6 but not ␣7 integrin. 3 Recently, Melchiori et al (38) have shown that transmigration of human 2/14 melanoma cells through the pores of a Boyden chamber coated with basement membrane proteins, using fibronectin, collagen IV, or laminin as chemoattractants, is inhibited by antibodies to ␣3 and ␤1 integrin chains. Increased expression of ␣3␤1 integrin has been also associated with enhanced tumor cell metastasis (39).…”

Section: Resultsmentioning

confidence: 99%

“…Undirected migration of cells over matrix-coated surfaces, in the absence of any concentration gradient, was termed haptotaxis (35,36), in contrast to chemotaxis which was described for cells migrating against a gradient of laminin or fibronectin fragments (37,38). Transmigration of cells through capillaries, basement membranes of epithelial tumors, or the matrixcovered filter of a Boyden chamber is, however, a more complex event than lateral locomotion on laminin-coated surfaces and may involve also other matrix-induced events such as proliferation and synthesis of proteases (40).…”

Section: Resultsmentioning

confidence: 99%

Specific Induction of Cell Motility on Laminin by α7 Integrin

Echtermeyer

Schober

Pöschl

et al. 1996

Journal of Biological Chemistry

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Laminin, the major glycoprotein of basement membranes, actively supports cell migration in development, tissue repair, tumor growth, metastasis, and other pathological processes. Previously we have shown that the locomotion of murine skeletal myoblasts is specifically and significantly enhanced on laminin but not on other matrix proteins. One of the major laminin receptors of myoblasts is the ␣7␤1 integrin, which was first described in human MeWo melanoma cells and Rugli glioblastoma cells. In order to investigate and directly test the role of the ␣7 integrin in cell migration on laminin, we expressed the murine ␣7B splice variant in human 293 kidney cells and 530 melanoma cells which cannot migrate on laminin and are devoid of endogenous ␣7. Northern blotting of the transfected cells showed that the ␣7 mRNA was expressed efficiently, and the protein was detected on the cell surface by immunofluorescence and fluorescence-activated cell sorter analysis. Cell motility measurements by computer-assisted time-lapse videomicroscopy of the ␣7-transfected cells revealed an 8 -10-fold increase in motility on laminin-1 and its E8 fragment, but not on fibronectin. Mock-transfected cells did not migrate significantly on laminin or on fibronectin. Similarly, transmigration of ␣7-transfected 293 cells through laminin-coated filters in a Boyden chamber assay was significantly enhanced in comparison to mocktransfected cells. These findings prove that ␣7 integrin expression confers a gain of function-motile phenotype to immobile cells and may be responsible for transduction of the laminin-induced cell motility.Cells utilize extracellular matrix to migrate during embryonic development, tissue regeneration, and invasion of tissues in inflammation and tumor metastasis (reviewed in Ref. 1). Laminin-1, a major glycoprotein of basement membranes, has been shown to promote migration of different cell types including neural crest cells (2), skeletal myoblasts (3), or B16 mouse melanoma cells (4). The mechanism of laminin-induced cell locomotion and the cellular receptors mediating the locomotor signals are, however, not known. Integrin-and non-integrin receptors are involved in the specific adhesion of cells to laminin. Dystroglycan, a 156-kDa protein forms a transmembrane linkage together with other proteins between laminin-2 and dystrophin in the muscle cell membrane (5); a high affinity laminin receptor of 67 kDa has been isolated from several tumor cells, myoblasts, and other primary cells (for reviews, see Refs. 6 -8). Five laminin-binding integrins of the ␤1 family recognize different sites and isoforms of laminin: ␣6␤1 (9, 10) and ␣7␤1 (11, 12) bind to laminin-1, recognizing specifically the E8 domain; ␣1␤1 binds to a cryptic site in the E1 region of laminin (13), but also to types I and IV collagen (14). The ␣3␤1 integrin binds to laminin-5 (kalinin) (15) and to other matrix proteins; ␣2␤1 is predominantly a collagen receptor (16), but when isolated from endothelial cells it also binds to laminin-1 (17).While much has been publi...

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“…Melanoma cells express αVβ3 integrin, which binds to fibronectin, vitronectin, collagen, laminin and integrin αVβ1, which selectively binds to fibronectin [85]. Indeed, in melanocytes or melanoma at early stages, the expression of the β3 integrin is undetectable, since β3 integrin has been shown to correlate with malignancy [86][87][88]. It is of note that αVβ3 is important for the adhesion of melanoma cells to dermal collagen and for the suppression of anoikis [89], mainly shifting the Bcl2:Bax ratio [90].…”

Section: Anoikis Resistance In Cancermentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

503

404

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Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

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The α3β1 Integrin Is Involved in Melanoma Cell Migration and Invasion

Cited by 118 publications

References 0 publications

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

Specific Induction of Cell Motility on Laminin by α7 Integrin

Anoikis: an emerging hallmark in health and diseases

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