Mcam Muc18 expression in melanomas

MUC-18 is a 113 kDa glycoprotein expressed on the cell surface. The gene MCAM encoding MUC-18 is a member of the immunoglobulin family. The MCAM glycoprotein is an adhesion molecule bearing homology to other cell adhesion molecules such as NCAM and ICAM and also to the DCC gene product (see page 177), as well as to MHC-2 and MHC-1. MCAM is found in some mesenchymal tissues, e.g. smooth muscle cells, endothelial cells and Schwann cells but not in epithelial or haemopoietic cells. MCAM is found consistently in mesenchymal neoplasms of both smooth muscle and endothelial origin and bears obvious relationship to malignancy with the exception that, although it is expressed consistently in neurofibromas and schanno-mas, it is not found in malignant peripheral nerve sheath tumours (Shih et al., 1996). Interestingly, MCAM is expressed in a subset of capillaries and tumour endothelia but it is not found in the endothelia of arteries or large veins (Sers et al., 1994). MCAM is not found in normal melanocytes or in benign cutaneous naevi, but it is highly expressed in malignant melanomas and metastatic lesions. MCAM-transfected cells show enhanced adhesion to endothelial cells and this is inhibited by antibodies to the MCAM glycoprotein. The MCAM-transfected cells also show differential adhesion to laminin and increased invasive ability in in vitro assays. These alterations in adhesive and invasive behaviour are reflected in enhanced metastatic ability (Huang et al, 1996). MCAM expression is up-regulated by transfection of melanoma cells by carcinoembryonic antigen (Grimm and Johnson, 1995) which is regarded as a good biomarker for total tumour burden (Sherbet, 1982). Huang et al. (1996) report that the MCAM transfectant cells also show enhanced expression of MMP-2, which might constitute the mechanism by which MCAM alters biological behaviour. The expression of MCAM is regulated by the transcription factor AP-2 which, incidentally, also regulates the genes coding for PAI, MMP-2, E-cadherin and insulin-like growth factors, and also the bcl-2 and c-kit genes. Thus, a concerted expression of several adhesion factors and metalloproteinases may be involved in the regulation of the invasive and metastatic behaviour of melanomas. Furthermore, the presence of the glycoprotein in tumour endothelia has been linked with endothelial proliferation, suggesting a close liaison with angiogenesis (Sers et al, 1994).

Another member of the family of immunoglobulin cell adhesion molecules is the basal cell adhesion molecule (BCAM). BCAM has the characteristic immunoglobulin domain structure and is closely related to MCAM (31% sequence homology) and to NCAM (Campbell et al., 1994).

BCAM promotes cell-matrix adhesion, as may be expected from the amino acid sequence homology it shares with MCAM and NCAM. It may be expressed in several normal tissues, both fetal and adult, but is also associated with malignant transformation of some cell types. A uniform expression of BCAM has been described in epithelial cancers of the ovary, but it is not found in non-epithelial ovarian cancer, or in lymphomas, sarcomas and tumours of neuroectodermal origin (Garinchesa et al., 1994).

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