GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer

• Published in: Current medical science Vol. 41; no. 3; pp. 522 - 528
• Main Authors: Mielcarska, Sylwia, Stopińska, Kamila, Dawidowicz, Miriam, Kula, Agnieszka, Kiczmer, Paweł, Seńkowska, Alicja Prawdzic, Zajdel, Ewa Nowakowska, Walkiewicz, Katarzyna, Waniczek, Dariusz, Świętochowska, Elżbieta
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.06.2021; Department of Medical and Molecular Biology,Faculty of Medical Sciences in Zabrze,Medical University of Silesia,Zabrze 41-808,Poland%Department and Chair of Pathomorphology,Faculty of Medical Sciences in Zabrze,Medical University of Silesia,Zabrze 41-800,Poland%Department of Nutrition Related Disease Prevention,Department of Metabolic Disease Prevention,School of Public Health in Bytom,Medical University of Silesia,Bytom 41-902,Poland%Department of Surgical Nursing and Surgery Propedeutics,Chair of General,Colorectal and Trauma Surgery,SHS in Katowice,Medical University of Silesia,Bytom 41-902,Poland
• Subjects: Aged; Cell Line, Tumor; Cell Proliferation - genetics; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; Growth Differentiation Factor 15 - genetics; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Neoplasm Staging; Neoplastic Stem Cells - pathology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Receptors, Chemokine - genetics; Tumor Microenvironment - genetics; Vascular Endothelial Growth Factor A - genetics; growth/differentiation factor 15 (GDF-15); chemokine-like receptor 1 (CMKLR1); colorectal cancer; VEGF-A; angiogenesis; growth/differentiation factor 15(GDF-15); chemokine-like receptor 1(CMKLR1)
• ISSN: 2096-5230; 1672-0733; 2523-899X; 1993-1352
• DOI: 10.1007/s11596-021-2335-0

Summary Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, responsible for over 880 000 deaths each year. Growth/differentiation factor 15 (GDF-15) is reported to be a promising diagnostic and prognostic factor in CRC. It induces pleiotropic effects in tumor cells: proliferation, stemness, invasion and metastasis. Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms. However, it has not been investigated in CRC yet. The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-1α (HIF-1α), VEGF-A and chemokine-like receptor 1 (CMKLR1) in tumor and margin specimens of CRC in relation to histological grade and TNM staging. The study comprised 33 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of GDF-15, HIF-1α, VEGF-A and CMKLR1, commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue. The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue. In CRC, the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α, VEGF A and CMKLR1 expression. Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC. The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors.