{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:02:11Z","timestamp":1790697731916,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. 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In the first variant, ALDOC overexpression promoted cell viability, adhesion to and transmigration through a layer of brain endothelial cells, and amplified brain micrometastasis formation. The cross\u2010talk between this MBM variant and microglia cells promoted the proliferation and migration of the latter cells. In sharp contrast, ALDOC overexpression in the second brain\u2010metastasizing melanoma variant reduced or did not affect the same malignancy features. In the third melanoma variant, ALDOC overexpression augmented certain characteristics of malignancy and reduced others. The analysis of biological functions and disease pathways in the ALDOC overexpressing variants clearly indicated that ALDOC induced the expression of tumor progression promoting genes in the first variant and antitumor progression properties in the second variant. Overall, these results accentuate the complex microenvironment interactions between microglia cells and MBM, and the functional impact of intertumor heterogeneity. Since intertumor\u00a0heterogeneity imposes a challenge in the planning of cancer treatment, we propose to employ the functional response of tumors with an identical histology, to a particular drug or the molecular signature of this response, as a predictive indicator of response\/nonresponse to this drug.<\/jats:p>","DOI":"10.1002\/1878-0261.12872","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T07:35:00Z","timestamp":1607067300000},"page":"1376-1390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The melanoma brain metastatic microenvironment: aldolase C partakes in shaping the malignant phenotype of melanoma cells \u2013 a case of inter\u2010tumor heterogeneity"],"prefix":"10.1002","volume":"15","author":[{"given":"Sivan","family":"Izraely","sequence":"first","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research George S. 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