Disease relevance of CD151

• Assessment of CD151 could be instrumental for improvements in lung cancer diagnosis and therapies [1].
• This is a first report describing about the relation between CD151 and colon cancer [2].
• However, among TM4SF, CD151 is identical to an existing gene, PETA-3, which may promote tumor metastasis of malignant cells, and its expression may be involved in the malignant progression of cancer [1].
• In beta4-deficient pyloric atresia associated with junctional epidermolysis bullosa (PA-JEB) keratinocytes, CD151 and alpha3beta1 are clustered together at the basal cell surface in association with patches of laminin-5 [3].
• We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease [4].

High impact information on CD151

• Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking the integrin alpha3 subunit die neonatally because of severe abnormalities in the lung and kidney epithelia [5].
• Our results support the hypothesis that CD151 plays a key role in strengthening alpha3beta1-mediated adhesion in podocytes [5].
• CD151, a member of the tetraspanin family proteins, tightly associates with integrin alpha3beta1 and localizes at basolateral surfaces of epithelial cells [6].
• CD151 regulates epithelial cell-cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization [6].
• E-Cadherin puncta formation, indicative of filopodia-based adhesion zipper formation, as well as E-cadherin anchorage to detergent-insoluble cytoskeletal matrix, was enhanced in CD151-overexpressing cells [6].

Biological context of CD151

• Clinical significance of CD151 gene expression in non-small cell lung cancer [1].
• Inhibition of cell migration was observed with antibodies to CD9, CD81, beta1, and alpha3, and, to a lesser extent, to CD151 [7].
• Taken together, these results indicate that the ligation of CD151 does not induce the up-regulation of integrin avidity, but might act as a component of integrin signalling complexes [8].
• The precise function of CD151 is unknown however complexes containing CD151 and beta1 integrins have been isolated from a number of cell systems and studies using anti-CD151 monoclonal antibodies have suggested a role in transmembrane signalling and cell adhesion [9].
• Transient transfection studies of PA-JEB cells with beta4 revealed that the integrin alpha6beta4 becomes incorporated into the alpha3beta1-CD151 clusters where it induces the formation of hemidesmosomes [3].

Anatomical context of CD151

• In contrast, reciprocal immunoprecipitations from various cell lines demonstrated that two other tetraspans, CD81 and CD151, formed complexes with integrins not disrupted by digitonin [10].
• F(ab')2 fragments of monoclonal antibodies (mAbs) against CD151 caused homotypic adhesion of HEL and K562 cells that was dependent on energy and cytoskeletal integrity and was augmented in the presence of RGDS peptides [8].
• We found accumulation of CD9, CD81, and CD151 together with alpha3 and beta1 integrins at intercellular junctions [7].
• Platelet-leukocyte interactions were assessed by using dual antibodies for a pan-platelet marker (CD151), together with CD14, a monocyte/macrophage marker [11].
• CD151 (PETA-3/SFA-1) is a member of the transmembrane 4 superfamily (TM4SF) of cell-surface proteins and is expressed abundantly both on the cell surface and in intracellular membranes by the haemopoietic cell lines M07e, HEL and K562 [8].

Chemical compound and disease context of CD151

• Analysis of alpha3 glycosylation in CD151-depleted breast cancer cells with reconstituted expression of various CD151 mutants has shown that a direct contact with integrin is required but not sufficient for the modulatory activity of the tetraspanin toward alpha3beta1 [12].

Associations of CD151 with chemical compounds

• In addition, CD151(-/-) platelets displayed normal "inside-out" integrin alpha(IIb)beta(3) signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol 1,4,5 triphosphate (IP(3)) levels [13].
• Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites [14].
• Simultaneous mutations of C11, C15, C242, and C243 (each to serine) eliminated >90% of CD151 palmitoylation [14].
• In contrast, weaker associations of CD151 with itself, integrins, or other tetraspanins (Triton X-100-sensitive but Brij 96-resistant) were independent of the QRD/TS151r site, occurred late in biosynthesis, and involved mature integrin subunits [15].
• Consistent with this possibility, engagement of CD151 by the substrate-adsorbed anti-CD151 mAb induced prominent Cdc42-dependent filopodial extension, which along with E-cadherin puncta formation, was strongly inhibited by calphostin C, a protein kinase C (PKC) inhibitor [6].
• The YXXvarphi motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins [16].
• A CD151 mutant with impaired association with alpha3beta1 integrin fails to restore junctional organization [17].

Physical interactions of CD151

• In the presence of mild detergent (CHAPS), CD151 co-immunoprecipitated with integrin alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha IIb beta 3 [8].
• CD151 forms a functional complex with c-Met in human salivary gland cancer cells [18].

Other interactions of CD151

• Altogether, these data suggest that, among tetraspans, CD81 interacts directly with the integrin alpha4beta1, and CD151 interacts directly with integrins alpha3beta1 and alpha6beta1 [10].
• CD63 and CD151 are largely expressed in the intracellular compartment, although some membrane expression is observed [7].
• RESULTS: In a drug free group, digestion of a single tablet of aspirin resulted in a significantly (p<0.05) diminished expression of PECAM-1, GP IIb, fibrinogen binding with PAC-1 antibody, GP Ib, P-selectin, and CD151 [11].
• Transmembrane 4 superfamily protein CD151 (PETA-3) associates with beta 1 and alpha IIb beta 3 integrins in haemopoietic cell lines and modulates cell-cell adhesion [8].
• The association of CD151 with alpha 4 beta 1 and alpha 5 beta 1 seemed to be constitutive, as it was not modified by treatment of M07e cells with cytokines that regulate integrin function by 'inside-out' signalling [8].

Analytical, diagnostic and therapeutic context of CD151

• On the basis of these results, we used reverse transcription-PCR and immunohistochemical techniques for a retrospective study of CD151 gene expression in tumor tissues from 145 lung cancer patients; 72 tumors were stage I, 29 stage II, 27 stage IIIA, and 17 stage IIIB [1].
• By immunoprecipitation from transfected K562 cells, we established that CD151 associates with alpha3beta1 and alpha6beta4 [3].
• Immunoelectron microscopy showed that CD151 is concentrated in hemidesmosomes [3].
• Immunoprecipitation/Western blot studies reveal a constitutive physical association of CD151 with integrin alpha(IIb)beta(3) complex under strong detergent conditions [13].
• Sequence analysis identified the antigen as PETA-3/CD151, a recently described member of the tetraspanin family of proteins [19].

References