GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer.
Aged
Cell Line, Tumor
Cell Proliferation
/ genetics
Colorectal Neoplasms
/ epidemiology
Female
Gene Expression Regulation, Neoplastic
Growth Differentiation Factor 15
/ genetics
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Male
Middle Aged
Neoplasm Invasiveness
/ genetics
Neoplasm Metastasis
Neoplasm Staging
Neoplastic Stem Cells
/ pathology
Neovascularization, Pathologic
/ genetics
Receptors, Chemokine
/ genetics
Tumor Microenvironment
/ genetics
Vascular Endothelial Growth Factor A
/ genetics
VEGF-A
angiogenesis
chemokine-like receptor 1 (CMKLR1)
colorectal cancer
growth/differentiation factor 15 (GDF-15)
Journal
Current medical science
ISSN: 2523-899X
Titre abrégé: Curr Med Sci
Pays: China
ID NLM: 101729993
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
28
06
2020
accepted:
19
11
2020
pubmed:
26
6
2021
medline:
24
12
2021
entrez:
25
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34169422
doi: 10.1007/s11596-021-2335-0
pii: 10.1007/s11596-021-2335-0
doi:
Substances chimiques
CMKLR1 protein, human
0
Growth Differentiation Factor 15
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Receptors, Chemokine
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
522-528Informations de copyright
© 2021. Huazhong University of Science and Technology.
Références
Cao D, Hou M, Guan Y-s, et al. Expression of HIF-lalpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications. BMC Cancer, 2009,9:432
doi: 10.1186/1471-2407-9-432
Fang L, Li F, Gu C. GDF-15: A Multifunctional Modulator and Potential Therapeutic Target in Cancer. Curr Pharm Des, 2019,25(6):654–662
doi: 10.2174/1381612825666190402101143
Minet E, Michel G, Remacle J, et al. Role of HIF-1 as a transcription factor involved in embryonic development, cancer progression and apoptosis (review). Int J Mol Med, 2000,5(3):253–259
pubmed: 10677565
Tamura R, Tanaka T, Akasaki Y, et al. The role of vascular endothelial growth factor in the hypoxic and immunosuppressive tumor microenvironment: perspectives for therapeutic implications. Med Oncol, 2019,37(1):2
doi: 10.1007/s12032-019-1329-2
Kiczmer P, Seńkowska AP, Kula A, et al. Assessment of CMKLR1 level in colorectal cancer and its correlation with angiogenic markers. Exp Mol Pathol, 2020,113: 104377
doi: 10.1016/j.yexmp.2020.104377
Zhang Y, Wang X, Zhang M, et al. GDF15 promotes epithelial-to-mesenchymal transition in colorectal corrected. Artif Cells Nanomed Biotechnol, 2018,46(sup2):652–658
doi: 10.1080/21691401.2018.1466146
McDougall SR, Anderson ARA, Chaplain MAJ. Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies. J Theor Biol, 2006,241(3):564–589
doi: 10.1016/j.jtbi.2005.12.022
Modi A, Dwivedi S, Roy D, et al. Growth differentiation factor 15 and its role in carcinogenesis: an update. Growth Factors, 2019,37(3–4):190–207
doi: 10.1080/08977194.2019.1685988
Zheng H, Wu Y, Guo T. Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling. Biomed Res Int, 2020,2020:5958272
pubmed: 32076610
pmcid: 7008299
Li C, Wang J, Kong J, et al. GDF15 promotes EMT and metastasis in colorectal cancer. Oncotarget, 2016,7(1): 860–872
doi: 10.18632/oncotarget.6205
Weber CE, Kuo PC. The tumor microenvironment. Surg Oncol, 2012,21(3):172–177
doi: 10.1016/j.suronc.2011.09.001
Rajaganeshan R, Prasad R, Guillou PJ, et al. Expression patterns of hypoxic markers at the invasive margin of colorectal cancers and liver metastases. Eur J Surg Oncol, 2009,35(12):1286–1294
doi: 10.1016/j.ejso.2009.05.008
Simonetti O, Lucarini G, Rubini C, et al. Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis. Oral Dis, 2013,19(6):620–627
doi: 10.1111/odi.12048
Oh SY, Kwon HC, Kim SH et al. Clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer. BMC Cancer, 2008,8:123
doi: 10.1186/1471-2407-8-123
Shen W, Li HL, Liu L, et al. Expression levels of PTEN, HIF-1α, and VEGF as prognostic factors in ovarian cancer. Eur Rev Med Pharmacol Sci, 2017,21(11):2596–2603
pubmed: 28678326
Takala H, Saarnio J, Wiik H, et al. HIF-1α and VEGF are associated with disease progression in esophageal carcinoma. J Surg Res, 2011,167(1):41–48
doi: 10.1016/j.jss.2009.11.725
Claesson-Welsh L, Welsh M. VEGFA and tumour angiogenesis. J Intern Med, 2013,273(2):114–127
doi: 10.1111/joim.12019
Takahashi T, Yamaguchi S, Chida K, et al. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J, 2001,20(11):2768–2778
doi: 10.1093/emboj/20.11.2768
Lindau D, Gielen P, Kroesen M, et al. The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology, 2013,138(2):105–115
doi: 10.1111/imm.12036
Seeber A, Gunsilius E, Gastl G. Anti-Angiogenics: Their Value in Colorectal Cancer Therapy. Oncol Res Treat, 2018,41(4):188–193
doi: 10.1159/000488301
Bruno T, Valerio M, Casadei L, et al. Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization. J Exp Clin Cancer Res, 2017,36(1):32
doi: 10.1186/s13046-017-0497-1
Wu Y, Jin M, Xu H, et al. Clinicopathologic significance of HIF-1α, CXCR4, and VEGF expression in colon cancer. Clin Dev Immunol, 2010,2010:537531
doi: 10.1155/2010/537531
Li C, Wang X, Casal I, et al. Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer. J Cell Mol Med, 2016,20(8):1420–1426
doi: 10.1111/jcmm.12830
Vocka M, Langer D, Fryba V, et al. Growth/differentiation factor 15 (GDF-15) as new potential serum marker in patients with metastatic colorectal cancer. Cancer Biomark, 2018,21(4):869–874
doi: 10.3233/CBM-170792
Wang W, Qi Y, Xu Q, et al. Expression and clinical significance of kisspeptin-1, matrix metalloproteinase-2 and vascular endothelial growth factor in tissue of colon cancer. Zhonghua Liu Xing Bing Xue Za Zhi (Chinese), 2016,37(3):415–417