Probing the interaction of tetraspanin CD151 with integrin α3β1 using a panel of monoclonal antibodies with distinct reactivities toward the CD151–integrin α3β1 complex

Yamada, Masashi; Tamura, Yoshio; Sanzen, Noriko; Sato-Nishiuchi, Ryoko; Hasegawa, Hitoshi; Ashman, Leonie K.; Rubinstein, Eric; Yáñez-Mó, Marı́a; Sánchez-Madrid, Francisco; Sekiguchi, Kiyotoshi

doi:10.1042/bj20071625

Cited by 24 publications

(17 citation statements)

References 34 publications

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“…Concordantly, in our system, CD151INF was able to mediate wild type levels of ␣3␤1 association with other tetraspanins and wild type ␣3␤1-dependent initial adhesion and motility on LM-332. Our data are consistent with a recent epitope mapping study showing that amino acids just upstream of the QRD motif are also involved in the Triton X-100-resistant CD151-␣3␤1 integrin interaction (43).…”

Section: Cd151 Domains Critical For ␣3␤1 Integrin-dependent Tumorsupporting

confidence: 82%

Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin

Zevian¹,

Winterwood²,

Stipp

2011

Journal of Biological Chemistry

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The basement membrane protein laminin-332 (laminin-5) mediates both stable cell adhesion and rapid cell migration and thus has the potential to either restrain or promote tumor cell metastasis. The major cellular receptors for laminin-332 are integrin ␣3␤1, which mediates rapid tumor cell migration, and integrin ␣6␤4, which often mediates stable cell attachment. Tetraspanin protein CD151 interacts directly with both ␣3␤1 and ␣6␤4 integrins and with other tetraspanins, thereby promoting ␣3␤1 and ␣6␤4 association with tetraspanin-enriched microdomains on the cell surface. To explore the possibility of selectively modulating tumor cell responses to laminin-332, we re-expressed a series of CD151 mutants in epidermoid carcinoma cells with near total, RNAi-mediated silencing of endogenous CD151. The interactions of CD151 with its integrin partners or its interactions with other tetraspanins were selectively disrupted by specific mutations in the CD151 large extracellular loop (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151-integrin association and CD151-tetraspanin association were both important for ␣3␤1 integrin-dependent initial adhesion and rapid migration on laminin-332. Remarkably, however, only CD151-integrin association was required for stable, ␣6␤4 integrin-dependent cell attachment on laminin-332. In addition, we found that a QRD amino acid motif in the CD151 EC2 domain, which had been thought to be crucial for CD151-integrin interaction, is not essential for CD151-integrin association or for the ability of CD151 to promote several different integrin functions. These new data suggest potential strategies for selectively modulating migratory cell responses to laminin-332, while leaving stable cell attachment on laminin-332 intact.CD151 is a member of the tetraspanin family of proteins, which possess four transmembrane domains, intracellular amino and carboxyl termini, and one small and one large extracellular domain (named EC1 and EC2, respectively). Tetraspanins share a unique cysteine motif in their EC2 domains that sets them apart from other four-pass proteins. Genetic deletion of CD151 results in defects in the maintenance of kidney and skin epithelial integrity, wound healing, platelet aggregation, and thrombus growth and stability, as well as reduced pathological angiogenesis (1-7). Analysis of clinical samples has revealed potential roles for CD151 in progression and metastasis of colon, prostate, lung, hepatocellular, and breast carcinomas (8 -14).Although CD151 function in platelets has been linked to the platelet integrin ␣IIb␤3 (3), the basis of CD151 functions in carcinomas and in normal epithelia may be its association with its major integrin partners ␣3␤1, ␣6␤1, and ␣6␤4. CD151 binds directly to these laminin-binding integrins in an interaction involving the CD151 EC2 domain and a membrane proximal region of the ␣ integrin subunit ectodomain. CD151 also associates with other tetraspanins, via a mechanism that depends on palmitoylation of membrane proximal intrace...

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Section: Cd151 Domains Critical For ␣3␤1 Integrin-dependent Tumorsupporting

confidence: 82%

Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin

Zevian¹,

Winterwood²,

Stipp

2011

Journal of Biological Chemistry

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“…These complexes are detected with different detergents, including digitonin and Triton X-100, which have been reported to disrupt tetraspanin-tetraspanin interactions. Moreover, the ability of the anti-CD151 mAbs to coimmunoprecipitate MT1-MMP correlates with their affinity for ␣3␤1-associated CD151, 27,39 FRET was readily detected with MT1-MMP/CD151 and ␣3␤1/CD151 pairs, but was very variable when MT1-MMP was cotransfected with the ␣3 integrin. This heterogeneous profile would support an indirect association for this pair, in which insertion into the same tetraspaninenriched microdomain might occasionally bring the 2 fluorescent tags close enough for FRET to occur.…”

Section: Discussionmentioning

confidence: 99%

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

Yáñez-Mó

Barreiro

Gonzalo

et al. 2008

Blood

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MT1-MMP plays IntroductionMT1-MMP is an important proteinase, with both direct actions on target substrates and indirect actions through its activation of a metalloproteinase cascade involving matrix metalloproteinase 2 (MMP2). Fibroblasts and tumor cells derived from MT1-MMPdeficient mice show impaired collagenolytic activity. 1 MT1-MMP is essential for bone maturation and lung development, but MT1-MMP function in other processes seems to be compensated in knockout mice by other metalloproteinases. 2 Supporting this, the phenotype of MMP2/MT1-MMP double-knockout mice is more severe, and these mice die in the first hours after birth. 3 MT1-MMP gene expression is regulated by signaling via ␤catenin/LEF4, Egr, NFAT, and Rac. Maturation by furin cleavage of the prodomain in MT1-MMP takes place intracellularly, so that the metalloproteinase is already mature when it reaches the plasma membrane. Hence, most regulation of MT1-MMP occurs at the plasma membrane. 4,5 MT1-MMP is inhibited by tissue inhibitors of matrix proteinases 2-4 (TIMPs 2-4), although TIMP2 is also necessary for the appropriate activation of MMP2 by MT1-MMP and forms a ternary complex with the 2 proteases. Other secreted proteins such as testican have also been shown to inhibit MT1-MMP activity. The membrane glycoprotein reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is an inhibitor of MT1-MMP, MMP2, and MMP9. 6 In addition, MT1-MMP activity is self-regulated by its autocatalytic processing, which removes the catalytic domain and may act as a negative regulatory mechanism. 7 Finally, MT1-MMP activity and turnover are regulated by hemopexin-dependent oligomerization. 8 Intracellular trafficking of MT1-MMP is necessary for its participation in cell migration and is thought to replenish the plasma membrane with active new MT1-MMP molecules via a Rab8-dependent exocytic pathway. 9 Thus, cells expressing MT1-MMP mutants, which fail to internalize, show enhanced MMP2 activation but a reduced invasive capability. 6 Internalization of MT1-MMP occurs both via the clathrin and the caveolae pathways, 10,11 and MT1-MMP internalization is regulated by its inclusion in lipid rafts. 12 Cell membrane tetraspanin-based microdomains are generated by lateral association of tetraspanin proteins with several other transmembrane proteins, including integrins and immunoglobulin (Ig) superfamily members. 13 Tetraspanins are key regulators of the functions and signaling activities of their associated partners in diverse cellular processes. Tetraspanin interactions have been reported for several proteases. For example, tetraspanin CD151 binds soluble pro-MMP7, facilitating its maturation. 14 However, only MT1-MMP 15 and some ADAM (A Disintegrin and Metalloproteinase) proteins 16,17 have been shown to be included in tetraspanin microdomains. Human umbilical vein endothelial cells (HUVECs) express a repertoire of tetraspanins, including CD9, CD81, and CD151, which are localized mainly at cell-cell junctions in association with ␣3␤1 integrin. 18 The tight stoi...

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“…Some of these mAbs were shown to display different patterns of binding to cells and tissues, depending on their ability or not to recognize CD151 when it is associated with integrins [45]. These differences were confirmed by CD151-integrin α3/β1 co-immunoprecipitation and epitope mapping studies [46].…”

Section: Anti-tumoral Activity Of Anti-cd151 Antibodiesmentioning

confidence: 92%

Tetraspanin CD151 as a target for antibody-based cancer immunotherapy

Haeuw

Goetsch

Bailly

et al. 2011

Biochemical Society Transactions

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CD151 is a plasma membrane protein belonging to the tetraspanin superfamily which is expressed on normal cells such as endothelial cells and platelets and frequently overexpressed on cancer cells. It is known to be functionally linked to cancer metastasis. In humans, increased expression of CD151 is indicative of a poor prognosis in different cancer types. Whereas its mechanism of action remains obscure, CD151 was shown to regulate cell motility and adhesion through association with laminin-binding integrins such as α3β1 or α6β4. Several anti-CD151 mAbs (monoclonal antibodies) have been shown to display anti-metastatic activity in vivo. Inhibition of metastasis was not attributed to any effect of these mAbs on tumour cell growth, but was essentially attributed to inhibition of cell motility. We have generated anti-CD151 mAbs which can inhibit the tumoral growth in different xenograft cancer models. As expected, these mAbs were also able to inhibit metastasis in orthotopic cancer models. These data suggest that CD151 could function at multiple cancer stages, including not only metastasis cascade steps, but also earlier steps of primary tumour growth, thus reinforcing the interest of this innovative target in oncology. mAbs targeting CD151 may be of significant interest for cancer biotherapy.

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Probing the interaction of tetraspanin CD151 with integrin α3β1 using a panel of monoclonal antibodies with distinct reactivities toward the CD151–integrin α3β1 complex

Cited by 24 publications

References 34 publications

Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin

Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

Tetraspanin CD151 as a target for antibody-based cancer immunotherapy

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