Original article Remodeling of the extracellular matrix in human uveal melanoma

Relevance. A key component of the tumor microenvironment is the extracellular matrix (ECM) – a network of macromolecules that maintain the integrity of tissues and organs. ECM remodeling during carcinogenesis represents a complex process of degradation and renewal of ECM components under the influence of factors secreted by tumor cells and matrix metalloproteinases (MMPs) produced by cancer-associated fibroblasts to stimulate the mechanisms of angiogenesis, metastasis, evasion of immune surveillance and drug resistance development. Studying the structural features and processes of ECM reorganization may contribute to the development of new approaches to the UM treatment. Purpose. Evaluation of the expression of markers associated with ECM remodeling in UM. Material and methods.The objects of the study were fragments of the post-equatorial zone of the choroid and tumors of patients’ eyes enucleated for medical reasons (n=15). Immunohistochemical staining of choroidal and tumor samples and analysis of the expression levels of proteins associated with ECM degradation (αSMA, Collagen type I, FN1, MMP2, MMP14, TIMP2) were performed. Results.An increase in the area of staining of αSMA(+) zones in the intratumoral region was shown. A decrease in the expression levels of collagen type I was noted. The studied tumor samples were characterized by a high expression of proteins associated with the degradation of the extracellular matrix – fibronectin, MMP2, MMP14 and TIMP2. Conclusion. The results obtained indicate an active process of ECM remodeling in UM, which may affect the invasive ability and metastatic spread of tumor cells. Key words: uveal melanoma, extracellular matrix, collagen, matrix metalloproteinases