The melanoma brain metastatic microenvironment: aldolase C partakes in shaping the malignant phenotype of melanoma cells - a case of inter-tumor heterogeneity

Autor: Isaac P. Witz, Sapir Malka, Alona Telerman, Matias A. Bustos, Romela Irene Ramos, Shlomit Ben-Menachem, Tsipi Meshel, Orit Sagi-Assif, Sivan Izraely, Dave S.B. Hoon, Metsada Pasmanik-Chor
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Skin Neoplasms
Cell Survival
Mice
Nude
microglia
Biology
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Cell Line
Tumor
Fructose-Bisphosphate Aldolase
Genetics
medicine
Tumor Microenvironment
melanoma
Animals
Humans
brain metastasis
Viability assay
neoplasms
RC254-282
Research Articles
Tumor microenvironment
Mice
Inbred BALB C
Microglia
Aldolase C
Brain Neoplasms
Melanoma
aldolase C
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
General Medicine
medicine.disease
030104 developmental biology
medicine.anatomical_structure
HEK293 Cells
Phenotype
Oncology
Biological Variation
Population
Tumor progression
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Brain metastasis
Research Article
Zdroj: Molecular Oncology
Molecular Oncology, Vol 15, Iss 5, Pp 1376-1390 (2021)
ISSN: 1878-0261
Popis: The melanoma‐microglia cross‐talk upregulates the expression of aldolase C (ALDOC) in melanoma cells from several patients. The response of melanoma cells from 2 different patients to ALDOC upregulation was diametrically divergent. Whereas several metastasis‐associated functions including brain metastasis formation were augmented in one melanoma cell line (Mel 1), these functions were attenuated in the other melanoma cell line (Mel 2).
Previous studies indicated that microglia cells upregulate the expression of aldolase C (ALDOC) in melanoma cells. The present study using brain‐metastasizing variants from three human melanomas explores the functional role of ALDOC in the formation and maintenance of melanoma brain metastasis (MBM). ALDOC overexpression impacted differentially the malignant phenotype of these three variants. 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‐talk 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‐metastasizing 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 heterogeneity 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.
Databáze: OpenAIRE
Externí odkaz: