Disease relevance of MCAM

• Protein levels of MCAM correlate with aggressive invasive behavior of melanoma cells in vitro and invivo [1].
• Cyclic AMP enhances the expression of an extravillous trophoblast marker, melanoma cell adhesion molecule, in choriocarcinoma cell JEG3 and human chorionic villous explant cultures [2].
• Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma [3].
• MUC18/MCAM is a melanoma-associated cell adhesion molecule that is also occasionally found on carcinomas and other tumor types [4].
• The growth behavior of 7 MCAM transfectants and their respective vector controls was evaluated in SCID mice [5].

High impact information on MCAM

• The sequence is most similar to MUC18, reported as a tumor progression marker in human melanoma [6].
• The cell surface glycoprotein MUC18, a member of the immunoglobulin superfamily and homologous to several cell adhesion molecules, is associated with tumor progression and the development of metastasis in human malignant melanoma [7].
• Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains [7].
• Sequencing of the putative MUC18 promoter region revealed a G + C-rich promoter lacking conventional TATA and CAAT boxes [7].
• These elements may contribute to the differential regulation of the MUC18 gene in normal and malignant tissues and suggest a role for this putative adhesion molecule in neural crest cells during embryonic development [7].

Chemical compound and disease context of MCAM

• Melanoma progression-associated glycoprotein MUC18/MCAM mediates homotypic cell adhesion through interaction with a heterophilic ligand [8].
• On the other hand, MCAM and beta(3) integrin are the two adhesion molecules that play a pivotal role in melanoma cell migration and invasion, and for this reason, may represent valuable targets for melanoma therapy [9].
• METHODS: CD146 was isolated from MEL-OH melanoma cells and characterized by Coomassie blue staining and Western blotting [10].
• Except for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken and it is significantly homologous with MUC18 a molecule involved in melanoma progression and metastasis in human beings [11].
• Using a combination of CAT reporter assays and semiquantitative reverse transcriptase-polymerase chain reaction, we observed that cyclic adenosine monophosphate significantly increases transcription of the melanoma cell adhesion molecule in nonmetastatic melanoma cells [12].

Biological context of MCAM

• The drug BQ788 is an endothelin-B (ET(B)) receptor antagonist and inhibits upregulation of MCAM by ET-1 [1].
• In this study, we demonstrated by immunohistochemistry that immunoreactive MCAM was not expressed on granulosa cells in the pre-ovulatory follicle, but it was clearly detected in large luteal cells in corpora lutea from the mid-luteal phase of the menstrual cycle [13].
• These results indicate that luteinizing granulosa cells express MCAM and that MCAM expression is regulated by LH/hCG and cytokines during luteinization [13].
• Assignment of the human melanoma cell adhesion molecule gene (MCAM) to chromosome 11 band q23.3 by radiation hybrid mapping [14].
• In addition, biochemical and pharmacological analysis revealed that CD146 engagement initiates the tyrosine phosphorylation of phospholipase C-gamma, Pyk2, and p130(Cas) [15].

Anatomical context of MCAM

• MUC18/MCAM (CD146), an activation antigen of human T lymphocytes [16].
• Endothelin-1 upregulates MCAM in melanocytes [1].
• Since MCAM has been reported to mediate cellular interaction with endothelial cells, this molecule may play a role in neovascularization during corpus luteum formation in the human ovary [13].
• MCAM expression on JEG3 cells, a human choriocarcinoma-derived cell line, was significantly enhanced when they were co-cultured with isolated human decidual tissue [2].
• Flow cytometry and Northern blot analysis revealed that MCAM expression on luteinizing granulosa cells was enhanced when the cells were cultured for 5 days in the presence of hCG (1 IU/ml) or cytokines such as interleukin-1alpha (10 ng/ml) and tumour necrosis factor-alpha (10 ng/ml) [13].

Associations of MCAM with chemical compounds

• Northern blotting analysis confirmed the expression of MCAM mRNA in corpus luteum [13].
• CD146 (S-Endo 1 Ag or MUC18) is a transmembrane glycoprotein expressed on endothelial cells on the whole vascular tree [15].
• Here we report that CD146 engagement by its specific monoclonal antibody in human umbilical vein endothelial cells induces a Ca(2+) influx that is sensitive to thapsigargin and EGTA treatment, indicating that CD146 engagement initiates a store-operated calcium mobilization [15].
• Adiponectin correlated significantly, in univariate analysis, with CD146 (r = 0.29, p = 0.009), thrombomodulin (r = 0.37, p = 0.001), protein Z (r = -0.25, p = 0.03), BMI (r = -0.26, p = 0.047), serum creatinine (r = 0.26, p = 0.02) and urea (r = 0.38, p = 0.001) [17].
• Phorbol ester and cyclic AMP-mediated regulation of the melanoma-associated cell adhesion molecule MUC18/MCAM [4].

Regulatory relationships of MCAM

• Our results show that Mader is preferentially expressed on neurons and glial cells and that the adhesion protein MUC18/MCAM is mainly expressed on vasculature within the CNS [18].
• Moreover, we found that CD146 dimerization was up-regulated by tumor conditional medium through the NF-kappa B pathway and down-regulated by mAb AA98 [19].

Other interactions of MCAM

• In addition, endothelin-3 (ET-3) and N-succinyl-[Glu9, Ala11, 15]-ET-1-1620, both selective ET(B) agonists, are potent upregulators of MCAM [1].
• The aim of this cross-sectional study was to evaluate possible relations between adiponectin, CD146, and other markers of endothelial cell injury in 82 stable kidney transplant recipients (mean age 45 years, mean time after transplantation 47 months) with and without CAD [17].
• Soluble CD146 was measured by competitive enzyme-linked immunosorbent assay in synovial fluids of 3 healthy individuals and 7 cadavers (controls), as wells as in patients with traumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthritis (PsA; n = 10), other non-RA polyarthritis (NRAP; n = 10), and RA (n = 31) [10].
• It correlated significantly, with PAI-1, thrombin-activatable fibrinolysis inhibitor, intercellular adhesion molecule, VCAM, and CD146 in nondiabetics on CAPD [20].
• Correlations between CD146 and adhesion molecules and TFPI might further support its use as a endothelial cell function marker [21].

Analytical, diagnostic and therapeutic context of MCAM

• The present investigation is focused on immunoelectron microscopical analysis of distribution patterns of CD146 adhesion molecules (MUC18 or MCAM) in the microenvironment of normal human thymus, using the pre-embedding indirect immunoperoxidase technique [22].
• Markers of endothelial cell activation/injury: CD146 and thrombomodulin are related to adiponectin in kidney allograft recipients [17].
• In multivariate regression analysis, only CD146 remained a positive predictor of adiponectin in all CAPD patients [20].
• The lineage-specific expression pattern of CD146 can be useful in the differential diagnosis of certain lesions including melanomas and various types of gestational trophoblastic lesions [23].
• METHODS: RT-PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues [24].

References