Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-? in melanoma cell cultures established from CNS lesions

Abstract

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‐γ 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‐γ 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. Int. J. Cancer 83:135–140, 1999. © 1999 Wiley‐Liss, Inc.

Neural Cell Adhesion Molecule Potentiates the Growth of Murine Melanoma via β-Catenin Signaling by Association with Fibroblast Growth Factor Receptor and Glycogen Synthase Kinase-3β

“…In contrast, the down-regulation of NCAM was observed in the development of colon cancer and some of myeloma (12,13) and all neuroblastoma (14), suggesting that the role of NCAM on tumor progression is largely dependent on tumor types. In melanoma, the earlier studies demonstrated that melanoma from central nervous system (CNS) metastases and non-CNS-derived metastases exhibit distinct levels of NCAM (15) and high expression of NCAM was detected in aggressive metastasizing uveal melanoma (16). In addition, we also found that NCAM facilitates the cellular invasion and metastasis in a recent study (17).…”

Desmoplastic Melanoma, Neurotropism, and Neurotrophin Receptors—What We Know and What We Do Not

“…104 Furthermore, in melanoma cell lines derived from central nervous system metastases, NCAM is constitutively expressed. 105 Despite these observations and the potential connection to PNI in other malignancies, to the best of our knowledge, we are not aware of any study that has investigated NCAM's relationship to PNI in melanoma. Enhanced expression of NCAM in DMs, in conjunction with studies demonstrating correlations with PNI in SCCs and pancreatic cancers suggest that such studies may be fruitful.…”

Neurotrophin Receptors and Perineural Invasion

“…Additionally, in vitro studies in melanoma cell lines have found expression of NCAM to be linked with secretion of MMP-2 and therefore enhanced invasiveness (Shi et al, 2011). Furthermore, in melanoma cell lines derived from central nervous system metastases, NCAM is constitutively expressed (Geertsen, Zenklusen, Kamarashev, Burg, & Dummer, 1999). Despite these observations and the potential connection to PNI in other malignancies, to the best of our knowledge, we are not aware of any study that has investigated NCAM's relationship to PNI in melanoma.…”