Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-gamma in melanoma cell cultures established from CNS lesions.
In advanced stages of malignant melanoma (MM), metastases to the CNS are frequently observed. Few results are available on trophic factors and immunological features involved in the process of invasion and adhesion of circulating metastatic cells into the CNS. A direct comparison of remote metastases found in different locations of the same patient might help to identify such properties. For this purpose, we screened a panel of MM cell cultures, which had been established from patients with surgically removed MM lesions of the CNS, for expression and regulation of immunorelevant molecules. The results were compared with standard controls and cultures established from non-CNS metastatic lesions of the same patients. No significant differences were observed for expression of HLA-I, HLA-II, ICAM-1 and the melanoma-associated antigens Mage-3, MelanA and tyrosinase. Constitutive expression of the neuronal cell adhesion molecule (NCAM) was found in all CNS-derived samples and in fewer than 50% of non-CNS derived cultures. IFN-gamma was found to have a weak up-regulating effect in all non-CNS-derived cultures, except normal melanocytes. However, in 6/7 CNS-derived cultures, pre-treatment with IFN-gamma reduced expression of NCAM to 28% to 77% of the level in untreated cultures. The presence and regulation of NCAM differs between MM cells derived from CNS metastases and non-CNS-derived melanocytic cells. Thus, NCAM might be a candidate immunoregulating molecule involved in the formation of CNS metastases of MM.
Geertsen
R
R
Department of Dermatology, University Hospital, Zürich, Switzerland.
Zenklusen
R
R
Kamarashev
J
J
Burg
G
G
Dummer
R
R
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015816:Cell Adhesion Molecules, Neuronal; D006680:HLA Antigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma