Disease relevance of CD82

• This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression [1].
• The expression of CD9, CD81 and CD82 was markedly down-regulated in basal cell carcinoma but not in Bowen's disease [2].
• CD82 may serve as a prognostic marker of metastasis in thyroid cancer [3].
• In contrast to CD82, CD63 mRNA and protein expression was unchanged in all thyroid carcinomas [3].
• All of the benign goiter tissues showed CD82 expression [3].

Psychiatry related information on CD82

• Similar to R3 peptide, R2 peptide also plays an important role in the formation of neurofibrillary tangles (NFTs) which is one of the two main biological characteristics of Alzheimer's disease (AD) [4].
• Combined with significant age and gender relations, this implies a risk of underdiagnosed depression, if the EORTC QLQ C33 is used as the only instrument to screen for psychological distress in cancer patients [5].

High impact information on CD82

• These results provide direct evidence that DARC is essential for the function of CD82 as a suppressor of metastasis [6].
• Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models [6].
• Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors [7].
• KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins [7].
• The virus-containing vacuoles were also labeled with antibodies against LAMP-1, CD81, and CD82, which were also incorporated into the viral envelope [8].

Chemical compound and disease context of CD82

• The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases) [3].
• To understand the basis of this association, we generated site-directed mutations in the various domains of CD82 and used coimmunoprecipitation and colocalization approaches to examine interactions with HTLV-1 MA [9].
• The structure of the KAI1 large extracellular domain was modeled based on the solved crystal structure of the extracellular domain of another tetraspanin superfamily protein member, CD81 (hepatitis C virus envelope E2 glycoprotein receptor) [10].
• Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissues from 53 bronchogenic adenocarcinomas and 51 squamous cell carcinomas using monoclonal antibodies against PTEN, nm23H-1, and KAI-1 proteins [11].
• In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression [12].

Biological context of CD82

• Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis [1].
• This down-regulation indicates that the diminished cell adhesiveness of CD82-expressing Du145 cells on laminin likely resulted from less cell surface expression of alpha6 integrins [13].
• Although the physiological relevance of this change is unknown, in vitro data show that ectopically expressed CD82/KAI-1 can suppress tumor cell migration, a process underlying the dissemination of tumor cells in vivo [5] [14].
• We further found that CD82 significantly inhibited cell adhesion on laminin 1 [13].
• After CD82 is expressed in Du145 cells, this cellular morphogenesis was abolished, indicating a functional cross-talk between CD82 and alpha6 integrins [13].

Anatomical context of CD82

• Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status [1].
• CD82, member of the tetra-span-transmembrane protein family, is a costimulatory protein for T cell activation [15].
• Here we demonstrate that two other tetraspans, CD82 and the early B cell marker CD9, are coimmunoprecipitated with CD19 from Brij97 lysates of B cell lines [16].
• CD82, tetra-span-transmembrane protein, is a regulated transducing molecule on U937 monocytic cell line [17].
• We have previously shown that CD82 membrane expression is up-regulated during differentiation of human monocytes [17].

Associations of CD82 with chemical compounds

• Finally, the internalization of cell surface integrin alpha6 is significantly enhanced upon CD82 expression [13].
• The present study addresses phenotypic changes in Chinese hamster ovary mutant cell line ldlD deficient in UDP-Glc 4-epimerase and expressing CD82 or CD9 by cDNA transfection [18].
• In contrast, mutations of conserved amino acids in the inner loop of CD82 or of palmitoylated cysteines that flank the inner loop diminished CD82 association with MA [9].
• Second, all functional effects linked to CD82 engagement, such as adhesion to culture plates, formation of actin bundles and early events of tyrosine phosphorylation, are abolished, or strongly reduced, by cholesterol depletion [19].
• Expression of CD82 causes a significant increase in the amount of EGFR and ErbB2 in the light fractions of the sucrose gradient [20].
• (iii) In contrast, YTS1 cells, lacking CD82, displayed HGF-independent activation of Met tyrosine kinase and high cell motility [21].

Physical interactions of CD82

• Expression of CD9, C63 and CD151 was found to be coupled whereas CD82 was expressed independently [22].
• CD82 could be coprecipitated with both mature and beta 2-microglobulin (beta 2m)-free heavy chains of MHC-I from CHAPS extracts [23].

Regulatory relationships of CD82

• Here we demonstrate that CD82 specifically attenuates ligand-induced dimerization of EGFR [20].
• These results indicate that CD82 co-stimulates T cells not only by sending intra-T cell signals that work synergistically with CD28 signals but also by inducing enhanced T cell-antigen-presenting cell interaction [24].
• Increased interaction of LFA-1 with ICAM-1 was further confirmed by enhanced adhesion of CD82-overexpressing Jurkat cells to immobilized ICAM-1-Ig [25].
• First, tetraspanin signaling induces a selective translocation of CD82 from detergent-resistant membrane fractions to the cytoskeleton-associated pellet [19].
• Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53 [26].

Other interactions of CD82

• No relationship was found between MRP-1 expression and KAI1 expression [27].
• Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs [27].
• In cells expressing CD82/KAI-1, the initial activation of EGFR is not affected, but subsequent desensitization of EGF-induced signaling occurs more rapidly [14].
• These associations were confirmed by the cocapping of CD19 with CD9 or CD82 [16].
• Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82 [28].

Analytical, diagnostic and therapeutic context of CD82

• Northern blot analysis showed quite variable expression of the CD82 gene among different organs [29].
• Co-immunoprecipitation experiments showed that, in the presence of CD82, uPAR preferentially formed stable associations with alpha(5)beta(1), but not with a variety of other integrins, including alpha(3)beta(1) [30].
• Subcellular fractionation, immunofluorescence microscopy, and immunoelectron microscopy showed that CD82 is highly enriched in MIICs, particularly in their internal membranes [31].
• Western blot analysis showed that VP-16 increased KAI1/CD82 protein expression obviously in various cancer cell lines, especially in those that were highly metastatic [32].
• Moreover, homotypic aggregation of the mutant src transfectant cells was not enhanced by KAI1/CD82 ligation with anti- CD82 antibody [33].

References