Regulation of integrin‐mediated adhesion to laminin and collagen in human melanocytes and in non‐metastatic and highly metastatic human melanoma cells

Danen, Erik H.J.; Muijen, G.N.P. van; Kemenade, E. van de Wiel-van; Jansen, Kees; Ruiter, Dirk J.; Figdor, Carl G.

doi:10.1002/ijc.2910540225

Cited by 66 publications

(53 citation statements)

References 30 publications

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“…8,9 Moreover, the cell surface expression levels of many integrins can be directly correlated with the metastatic potential of melanoma cells. [10][11][12] Modulation of the actin cytoskeleton is critical for integrin function and tumor cell migration and invasion. 13 Changes in the actin cytoskeleton are accomplished by a variety of actin-binding proteins such as cofilin, a-actinin, filamin and plastin.…”

mentioning

confidence: 99%

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Klemke

Rafael

Wabnitz

et al. 2007

Intl Journal of Cancer

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The leukocyte specific actin-binding protein L-plastin is aberrantly expressed in several nonhematopoetic malignant tumors. However, little is known about the functional consequences of Lplastin expression. Here, we investigated the function of L-plastin in human malignant melanoma cells. Knock-down of endogenous L-plastin by siRNA treatment reduced migration of the melanoma cell line IF6. However, in melanoma patients, no correlation existed between L-plastin expression and tumor stages. This implied that additional factors such as phosphorylation of L-plastin may influence its function in tumor cells. To investigate this further, EGFP-tagged wild-type L-plastin (wt-LPL-EGFP) and a mutated, nonphosphorylatable L-plastin protein (5A7A-LPL-EGFP), were expressed in the L-plastin negative melanoma cell line MV3. Biochemical analysis revealed that wt-LPL-EGFP is phosphorylated in MV3 cells while 5A7A-LPL-EGFP is not. Although both wt-LPL-EGFP and 5A7A-LPL-EGFP were targeted to, and promote the formation of, vinculin-containing adhesion sites, static adhesion to either Matrigel or isolated extracellular matrix molecules was neither influenced by expression of wt-LPL-EGFP nor by expression of 5A7A-LPL-EGFP when compared with EGFP expressing control cells. In contrast, haptotactic, but not chemotactic, migration of melanoma cells towards either Matrigel or isolated extracellular matrix molecules was similarly enhanced, if either 5A7A-LPL-EGFP or wt-LPL-EGFP were expressed in MV3 cells. Interestingly, only cells expressing the phosphorylatable wt-LPL-EGFP protein showed enhanced invasion into Matrigel. In line with these findings the in vivo metastatic capacity of mouse B16 melanoma cells correlates with expression and phosphorylation of L-plastin. These data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L-plastin. ' 2007 Wiley-Liss, Inc.Key words: migration; invasion; adhesion; L-plastin; melanoma Malignant melanoma is a very aggressive type of cancer that frequently metastasizes to distant organs. The capacity of tumor cells to form metastatic foci correlates with the ability to proteolytically degrade basement membrane barriers and to adhere to and migrate through extracellular matrix layers. 1,2 Two classes of molecules are mainly involved in these processes: the matrix metalloproteinases (MMPs) 3 and integrins. 4,5 Integrins are a large family of adhesion receptors involved in cell-cell and cellextracellular matrix interactions. They consist of heterodimers of 2 noncovalently associated a-and b-subunits. 6 The role of integrins in tumor cell metastasis has been intensively studied. 4,5,7 In human melanoma, especially b1-and b3-subunit containing integrins play important roles in metastasis, through an enhancement of adhesion, migration and invasion. 8,9 Moreover, the cell surface expression levels of many integrins can be directly correlated with the metastatic potential of melanoma cells. [10][11][12] Modulation of the actin cytoskeleton is critical f...

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confidence: 99%

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Klemke

Rafael

Wabnitz

et al. 2007

Intl Journal of Cancer

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“…Adhesion assays were performed as described previously by Danen et al 26 and briefly recaptulated below. Ninety-six well flat-bottom microtitre plates were coated with 20 mg/mL of one of the following: human plasma-derived laminin (Sigma), human foreskin fibroblast-derived fibronectin (Sigma), human placental collagen IV (Sigma), rooster combderived hyaluronic acid (Sigma) or human glioblastoma cell line-derived tenascin (Sigma).…”

Section: Adhesion Assaysmentioning

confidence: 99%

Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion

Poole

Wijngaard

Westerhof³

et al. 1997

British Journal of Dermatology

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SummaryThe aetiology of vitiligo remains obscure. In this study, the role of integrins in the observed inability of melanocytes to repopulate lesional skin was investigated. Antibodies directed to a 2 , a 3 , a 5 , a v , a 6 , b 1 and b 3 integrin subunits were used. Immunohistology revealed no marked differences in the overall levels of expression of integrins between control, non-lesional, perilesional or lesional skin. Moreover, no differences were noted in the level of expression of integrins or the adhesive capacity between cultured control cells derived from three separate donors and vitiligo-derived melanocytes from two donors. Rather, it was clearly observed that towards the lesion, vitiligo skin contains increasing amounts of tenascin in the basal membrane and papillary dermis in five patients employing T2H5 antihuman tenascin antibody. The anti-adhesive effect observed in vitro for this extracellular matrix molecule using normal melanocytes may contribute to loss of pigment cells in vitiligo or to ineffective repopulation of the lesions.In vitiligo, melanocytes are gradually lost in depigmenting lesions of the skin. 1 It has been suggested that defective adhesion is involved in loss of melanocytes in this pigmentary disorder. 2 Moreover, the persistence of depigmented lesions is suggestive of defective melanocyte migration which may be reversed by photochemotherapy, 2 and therefore baseline expression of adhesion molecules may differ in vitiligo as compared with control skin. Melanocyte adhesion, spreading and migration is mediated by integrins. 3 Employing antibodies to integrin subunits, the specific integrins involved in each process have been identified in vitro. 3,4 Importantly, all integrins thus far identified on melanocytes can also be found on neighbouring keratinocytes. Although immunohistology has been employed to identify integrins expressed on melanocytes in situ per se, 3 this may not be the method of choice to determine differences in the level of expression by melanocytes. Even by double immunostaining procedures, it is difficult to distinguish between integrin expression by melanocytes vs. neighbouring keratinocytes. Therefore, in vitro cultures derived from control as well as from vitiligo non-lesional skin were employed to investigate further potential differences in adhesive behaviour in vitiligo and control skin. In addition, the use of cultured cells provides the opportunity to perform functional adhesion assays. In this respect it is of great interest to note that cultured melanocytes from nonlesional vitiligo skin appear to retain disease-related characteristics. It has been demonstrated that vitiligo melanocytes have altered growth characteristics under limiting conditions. 5 Moreover, upon electron microscopic observation, dilated rough endoplasmic reticulum (RER) is apparent in diseased cells from human and mouse vitiligo subjects. 6,7 Therefore, the use of cultured cells to investigate differences in adhesive characteristics is justified.The level of expression of relevant i...

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“…Strong evidence was presented for α2β1 integrin as the most specific receptor for collagen type I and highly expressed on the melanoma cells. [7][8][9][10] This integrin was reported to be especially important as a mediator of melanoma cell adhesion and migration in vitro and metastasis in vivo in experimental mouse models. Therefore, α2β1 integrin was identified as a melanoma progression antigen, which interacts with collagen, laminin and fibronectin.…”

Section: Introductionmentioning

confidence: 99%

Effect of VP12 and viperistatin on inhibition of collagen receptors: dependent melanoma metastasis

Staniszewska

Walsh²,

Rothman³

et al. 2009

Cancer Biology & Therapy

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Cancer Biology & Therapy 1507 VP12 and viperistatin inhibit melanoma metastasisViperistatin and VP12 isolated from Vipera paleastinae venom showed a potent inhibitory activity against collagen receptors, α1β1 and α2β1 integrins, respectively. Structurally, viperistatin belongs to the disintegrin family of proteins, whereas VP12 is composed of two subunits VP12A and VP12B displaying amino acid sequence homology with heterodimeric C-lectin type proteins. Viperistatin and VP12 used separately and simultaneously inhibited pro-metastatic activities of melanoma cells lines. The level of inhibition of MV3 and HS.939T human cell lines in cell adhesion and migration assays by both compounds was correlated with expression of α1β1 and α2β1 integrins on the cell surface. MV3 cells express collagen receptors to much higher extent than HS.939T and required the application of higher concentrations of inhibitors to block their adhesion to collagen types I and IV. A melanoma cell transmigration assay through a dHMVEC layer revealed that α1β1 integrin plays a significant role in invasion of HS.939T cells, while α2β1 integrin appears to be more important for MV3 cells. In an animal model of hematogenous metastasis of the mouse B16F10 cell line, the inhibitory effect of viperistatin and VP12 was only partial. These data suggest that collagen receptors may be an interesting target for development of new anti-metastatic therapies.

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Regulation of integrin‐mediated adhesion to laminin and collagen in human melanocytes and in non‐metastatic and highly metastatic human melanoma cells

Cited by 66 publications

References 30 publications

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion

Effect of VP12 and viperistatin on inhibition of collagen receptors: dependent melanoma metastasis

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