Examination of the expression of both the MUC18 mRNA and of the glycoprotein on the cell surface revealed a statistically significant correlation (P = 0.040) between its expression and the ability to form metastases in vivo.
We demonstrate here that human T cells, upon activation, neo-express the melanoma metastasis-associated surface molecule MUC18/melanoma cell adhesion molecule (MCAM).
In addition, the cell-surface adhesion molecule MCAM/MUC18 that is involved in metastasis of human melanoma was downregulated in the KCREB-transfected cells.
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.
The influence of MCAM expression on lung metastases formation in an experimental metastasis assay was system dependent, converting only XP44RO(Mel) transfectants into metastatic cells, although increased homotypic adhesion, leading to formation of tumor cell clusters, was observed with transfectants of both cell lines in vitro.
In nonmetastatic cells, however, melanoma cell adhesion molecule expression is repressed and we speculate that stem cell factor/c-Kit signaling might be responsible for the control of melanoma cell adhesion molecule synthesis, and thus, perhaps, of melanoma progression and metastasis.
Alteration in the expression of invasion/metastasis-related melanoma cell adhesion molecule (MelCAM) is strongly associated with the acquisition of malignancy by human melanoma.
Since E-cadherin is a melanoma invasion suppressor, and MCAM is a melanoma invasion promoter, ET-1 may promote melanoma invasion and metastasis through the regulation of adhesion molecule expression.
The G418-resistant (G418R)-LNCaP clones that expressed a high level of huMUC18 were selected and used for testing the effect of huMUC18 expression on the in vitro growth, motility, and invasiveness as well as on the in vivo metastasis (via orthotopical injection) in a xenograft nude mouse model.
A subset of host B lymphocytes controls melanoma metastasis through a melanoma cell adhesion molecule/MUC18-dependent interaction: evidence from mice and humans.
To our knowledge, this is the first demonstration that MUC18 is involved in cell signaling regulating the expression of Id-1 and ATF-3, thus contributing to melanoma metastasis.
Loss of AP-2α and overexpression of CREB/ATF-1 results in the overexpression of MCAM/MUC18 which by itself contributes to melanoma metastasis by regulating the inhibitor of DNA binding-1 (Id-1).
An orthotopic breast tumor model demonstrated that CD146-overexpressing breast tumors showed a poorly differentiated phenotype and displayed increased tumor invasion and metastasis.
Antagonistic effects of JAM-A, a tight junction-associated protein, on CD146 promigratory effects underline the complexity of the adhesion molecules network in tumor cell migration and metastasis.
The level of its expression has been found to correlate directly with tumour progression and metastatic potential, thus establishing CD146 as an important candidate of tumour growth and metastasis.
Positive CD146 expression, and average microvessel and lymph vessel counts were also significantly lower in cases with well-differentiated adenocarcinoma, maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues than in cases with poorly differentiated adenocarcinoma, maximal tumor diameter ≥ 2 cm, metastasis in lymph nodes, and invasion of regional tissues (p < 0.05 or p < 0.01).
MCAM is likely to participate in the regulation of the Rho signalling pathway to protect ovarian cancer cells from apoptosis and promote their malignant invasion and metastasis.
Cell surface glycoprotein MUC18 (alias CD146 or melanoma cell adhesion molecule) has been shown to promote metastasis in several tumors, including melanoma.
In tumor metastasis PCR microarray, 24 genes related to cell invading, adhesion, cellular growth and differentiation were found with a twofold difference between SW1116-S5 and SW1116-M. Sixteen of these, including E-cadherins, MTSS1, TRAIL and TRPM1, were up-regulated; eight genes including cathepsin L, EphB2, HGF, MET, MCAM and RORβ were down-regulated.
To mimic physiological situations, we used pooled METCAM/MUC18-expressing and control (vector) clones for testing effects of human METCAM/MUC18 over-expression on in vitro motility and invasiveness, and on in vivo tumor formation and metastasis in female athymic nude mice.