Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MUC18 antigen is an integral membrane glycoprotein of 113 kDa whose expression on primary human melanomas correlates with poor prognosis and the development of metastatic disease. MUC18 is expressed only sporadically in benign melanocytic nevi and thin primary melanomas that have a low probability of metastasizing. However, with increasing tumor thickness, MUC18 expression becomes more frequent and it is found on 80% of advanced primary tumors and metastases. MUC18-encoding cDNA clones were obtained by screening a human melanoma phage lambda expression library with monoclonal antibodies produced against the denatured antigen. The deduced sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N-CAM). The close structural relationship with these molecules suggests that MUC18 may also be a developmentally regulated cell adhesion molecule.
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PMID:MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. 260 81

The present study describes two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000, which are associated with the transformed phenotype of melanocytes. The monoclonal antibodies (MoAb) MUC18 and MUC54, raised against human malignant melanoma, were selected for differential reactivity with normal and neoplastic cells of melanocyte lineage. The antigen defined by MoAb MUC18 is a membrane bound monomeric sialylated glycoprotein with an apparent molecular weight of 113,000. In contrast to the broad reactivity with melanomas, isolated nevus nests were stained in only 1 of 55 nevi investigated. No staining of MoAb MUC18 was observed in a large variety of surgically removed normal and tumor tissues except for smooth muscle cells of the blood vessel wall and hair follicles. MoAb MUC54 immunoprecipitated a cytoplasmic monomeric protein with an apparent molecular weight of 76,000. By immunoperoxidase staining, the antigen was demonstrated on a large number of melanomas and in addition on 1 of 36 nevocellular, 3 of 4 Spitz, and 5 of 14 dysplastic nevi. The Mr 76,000 protein was found in a number of epithelial tissues and various types of neoplasms. Both antibodies presented in this study define structural changes in the antigenic profile of melanocytes occurring during carcinogenesis.
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PMID:Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. 354 95

The cell-cell adhesion receptor, Mel-CAM/MUC18, is highly expressed on metastatic melanoma cells and is also detectable on primary melanomas but not on normal melanocytes. Previous studies have shown that increased Mel-CAM/MUC18 expression correlates with tumor thickness and metastatic potential. We show here that normal melanocytes and nevus cells in culture express Mel-CAM/MUC18, but expression is down-regulated when cells are co-cultured with keratinocytes. Such keratinocyte-mediated regulation of Mel-CAM/MUC18 expression on melanocytes, nevus cells, and early melanomas can also be demonstrated in situ in patients' specimens. On the other hand, melanoma cells from primary and metastatic lesions constitutively express Mel-CAM/MUC18, and keratinocytes have no modulatory effect. These results suggest that contact between keratinocytes and human melanocytic cells modulates Mel-CAM/MUC18 expression, raising the possibility that escape from keratinocyte control during melanoma development leads to expression of antigens that contribute to the malignant phenotype.
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PMID:Regulation of Mel-CAM/MUC18 expression on melanocytes of different stages of tumor progression by normal keratinocytes. 794 74

Cell surface melanoma-associated antigens can mediate cell-cell or cell-substrate adhesion, signal transduction, proteolysis, or immune recognition and play a key role in determining invasive and metastatic competence of the tumor cells. The melanoma-associated antigen, A32, was defined by a murine monoclonal antibody and was immunoprecipitated as a single 113 kDa integral membrane glycoprotein containing sialic acid and HNK-1 carbohydrate moieties. Immunohistochemistry revealed the presence of A32 antigen on most melanomas and nevi but not on normal epidermal melanocytes. Of the normal tissues tested, only endothelium, smooth muscle, cerebellum, and hair follicles expressed the A32 antigen. Tryptic peptides of the A32 antigen obtained after immunoaffinity chromatography showed sequence identity to MUC18 antigen, a member of the immunoglobulin supergene family. Melanoma cells adhered to affinity-purified A32 antigen immobilized to a solid phase, and the adhesion was blocked by either soluble A32 antigen or monoclonal antibody against the HNK-1 carbohydrate moiety. These findings, together with the observation that A32 antigen is concentrated in cell-cell contact borders, suggest that this antigen is an adhesion molecule with a possible role in tumor invasion and metastasis.
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PMID:Isolation and functional characterization of the A32 melanoma-associated antigen. 816 2

Atypical (dysplastic) nevi are melanocytic lesions, which are precursors of melanoma as well as markers of increased melanoma risk. Although these lesions exhibit distinct clinical and histological features, their molecular features are largely unknown. To determine whether atypical, compared to benign nevi, from patients with a clinical history of malignant melanoma reveal molecular changes, we analyzed these lesions for the expression of two growth factors (basic fibroblast growth factor and transforming growth factor alpha), their receptors (fibroblast growth factor receptor-1 and epidermal growth factor receptor), and two cell adhesion molecules (MUC18 and alpha v beta 3 integrin), all of which are expressed in primary and metastatic melanomas. The results demonstrated a statistically significant correlation (P = 0.02) between increasing degrees of histological atypia and expression of epidermal growth factor receptor in the epidermal keratinocytes of atypical melanocytic lesions. Furthermore, both atypical and benign nevi revealed considerably high levels of overall gene activity in their dermal melanocytic and epidermal keratinocytic compartments. In contrast, the epidermal-dermal junction wherein melanoma evolves showed little gene activity, suggesting that molecular events occurring adjacent to this junction may be important for melanocytic transformation.
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PMID:Molecular analysis of melanoma precursor lesions. 895 42

The cell surface adhesion molecule MCAM (MUC18) is strongly expressed by advanced primary and metastatic melanomas but is weaker and less frequent in nevus cells. Previous studies have shown that MCAM expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. To provide direct evidence that MCAM plays a role in tumor growth and metastasis of human melanoma, the nonmetastatic MCAM-negative primary cutaneous melanoma SB-2 cells were transfected with MCAM cDNA and analyzed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MCAM in SB-2 cells rendered them highly tumorigenic and increased their metastatic potential in nude mice as compared with parental and control transfected cells. The transfected cells displayed increased homotypic adhesion, increased attachment to human endothelial cells, decreased ability to adhere to laminin, and increased invasiveness through Matrigel-coated filters. Anti-MCAM monoclonal antibody reversed these functions in the transfected cells but not in control cells. The above changes in function attributed to the expression of MCAM may underlie the contribution of MCAM/MUC18 to the malignant phenotype.
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PMID:Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. 918 35

Desmoplastic/spindle cell melanoma is a rare variant of melanoma. A number of factors complicate the diagnosis of desmoplastic/spindle cell melanoma, including the variable absence of a lentiginous component, its spindle cell morphology, and its many morphologic mimics, including scars, malignant peripheral nerve sheath tumor, neurofibroma, atypical fibroxanthoma, and spindled carcinoma. The immunohistochemical confirmation of desmoplastic/spindle cell melanoma may also be difficult, because the majority of tumors are negative for specific melanocytic markers such as HMB-45 and Melan-A, despite their usual expression of S-100 protein. Two new and potentially promising melanocytic markers, microphthalmia transcription factor (MiTF) and melanoma cell adhesion molecule (Mel-CAM), have been shown to be sensitive markers of epithelioid melanoma, but have not been tested in desmoplastic/spindle cell melanoma or in other rare melanocytic neuroectodermal tumors such as clear cell sarcoma. We immunostained 79 tumors (20 desmoplastic/spindle cell melanomas, 10 scars, 10 neurofibromas, 12 malignant peripheral nerve sheath tumors, 10 atypical fibroxanthomas, 10 clear cell sarcomas, 3 melanotic schwannomas, and 4 cellular blue nevi) for MiTF and Mel-CAM. MiTF expression was seen in 11 of 20 desmoplastic/spindle cell melanomas, 0 of 10 scars, 2 of 10 neurofibromas, 0 of 12 malignant peripheral nerve sheath tumors, 1 of 10 atypical fibroxanthomas, 7 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 3 of 4 cellular blue nevi. Mel-CAM expression was present in 14 of 17 desmoplastic/spindle cell melanomas, 0 of 10 scars, 4 of 10 neurofibromas, 3 of 11 malignant peripheral nerve sheath tumors, 0 of 10 atypical fibroxanthomas, 9 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 0 of 4 cellular blue nevi. MiTF and Mel-CAM were coexpressed in 6 of 17 desmoplastic/spindle cell melanomas and in no other tumor. Regarding desmoplastic/spindle cell melanoma, scar, neurofibroma, malignant peripheral nerve sheath tumor, and atypical fibroxanthoma, the sensitivity and specificity of MiTF for desmoplastic/spindle cell melanoma were 55% and 91%, respectively. For this same group of tumors, Mel-CAM had a sensitivity of 82% and a specificity of 83%. We conclude that the sensitivity and specificity of MiTF for desmoplastic melanoma equals or exceeds that of such markers as HMB-45 or Melan-A, and that MiTF should be part of the initial immunohistochemical panel for the work-up of such cases. Mel-CAM, while very sensitive, is relatively nonspecific, because it is also expressed in a variety of mesenchymal tumors and carcinomas. Mel-CAM is best reserved for cases morphologically suspected to be desmoplastic/ spindle cell melanoma, in which S-100 is positive and MiTF and other melanocytic markers are negative. These markers may also be helpful in certain other differential diagnoses, such as distinguishing clear cell sarcomas from epithelioid malignant peripheral nerve sheath tumors.
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PMID:Microphthalmia transcription factor and melanoma cell adhesion molecule expression distinguish desmoplastic/spindle cell melanoma from morphologic mimics. 1114 52