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192 Cross-Talk with the Microenvironment: The Case of Melanoma Brain Metastasis

Witz, Isaac P2; Izraelya, Sivan1; Kleina, Anat1; Sagi-Assifa, Orit1

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 81
doi: 10.1097/01.qai.0000397374.93448.27

1Dept. Cell Research and Immunology, Tel Aviv University, Tel Aviv Israel; and 2Institute of Human Virology

Various non-tumor cells in the tumor microenvironment including lymphocytes, macrophages, fibroblasts, endothelial cells and their soluble products shape the malignancy phenotype of the tumor and drive its progression towards metastasis.

This presentation deals with interactions of the brain microenvironment with brain metastasizing melanoma cells.

Brain metastasis confers upon melanoma patients an extremely bad prognosis. The mechanisms underlying homing to and survival of metastatic melanoma cells in the brain are unknown. Our working hypothesis is that interactions of melanoma cells with the brain microenvironment regulate site specific metastasis to this organ.

We generated, from single human melanomas variants that form either local cutaneous tumors or brain metastasis in xenografted nude mice. As these variants have identical genetic backgrounds, any molecular differences between them reflect, most probably, alterations associated with the ability to form brain metastasis. These variants are used to establish a specific molecular signature of melanoma brain metastasis.

Utilizing microarrays, we generated gene expression profiles of the cutaneous and brain-metastasizing melanoma variants. This analysis revealed a set of genes differentially expressed in local and metastatic variants. Surface molecules associated with tumor progression were also found to be differentially expressed on local and metastatic variants.

The two types of variants react differently to signals delivered by the brain microenvironment. This differential reactivity of certain melanoma variants with the brain microenvironment may account for the propensity of such variants to specifically metastasize to this organ site.

This study was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Needham, MA, USA)

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.