ADIPOSE TISSUE AND ITS ROLE IN MICROENVIRONMENT OF THE COLORECTAL ADENOCARCINOMA CANCER CELL
DOI:
https://doi.org/10.11603/ijmmr.2413-6077.2019.1.9819Keywords:
locally advanced rectal cancer, adipose tissue, tumor progression, chemoradiotherapyAbstract
Introduction. The mechanisms of adipose-tissue’s influence on tumor progression has been studied a lot, but the way of interaction of adipocytes with tumor cells have not been well defined until now.
Objective. The aim of this study was to evaluate the mechanisms of adipocytes and tumor cells interaction under the influence of radiation and chemo-radiation therapy in locally advanced rectal cancer (LARC) patients.
Material and methods. A prospective randomized single-center study was conducted. It involved 110 patients with LARC and pre-obesity. The patients were randomized into a main group A (radiation therapy and oxaliplatin-based chemotherapy) and a comparison group B (radiation therapy and fluoropyrimidine-based mono-chemotherapy). Superoxide free radicals and NO levels generated by mitochondria of adipocytes were evaluated In both groups’. Also, there was estimated the indices of MMP-2, MMP-9, 8-oxoG, and free fatty acids (FFA) level.
Results and discussion. Level of superoxide radicals in tumor-adjacent adipose tissue was 0.58±0.15 (main group) and 0.70±0.12 nmol/g·min (comparison group) (p<0.001). Blood levels of FFA increased in group A up to 2.05±0.15, and in group B up to 2.48±0.20 mmol/l (while in it was 0.57±0.11 mmol/L). 8-oxoG levels in tumor-adjacent adipose tissue had no statistically significant differences.
Conclusions. The tumor-adjacent adipose tissue is an energy depot that can act as a promoter of tumor progression supplying the locally advanced rectal cancer with an energy substrate FFA. It has been established that the level MMP-2 activity significantly reduces the degree of intercellular matrix remodeling by the XELOX chemotherapy.
References
Currie E, Schulze A, Zechner R, Walther TC, Farese Jr RV. Cellular fatty acid metabolism and cancer. Cell metabolism. 2013 Aug 6;18(2):153-61.
doi: 10.1016/j.cmet.2013.05.017 DOI: https://doi.org/10.1016/j.cmet.2013.05.017
Daniëls VW, Smans K, Royaux I, Chypre M, Swinnen JV, Zaidi N. Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. PloS one. 2014 Sep 12;9(9):e106913.
doi: 10.1371/journal.pone.0106913 DOI: https://doi.org/10.1371/journal.pone.0106913
Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell metabolism. 2012 Jan 4;15(1):4-5.
doi: 10.1016/j.cmet.2011.12.011 DOI: https://doi.org/10.1016/j.cmet.2011.12.011
Manzi L, Costantini L, Molinari R, Merendino N. Effect of dietary omega-3 polyunsaturated fatty acid DHA on glycolytic enzymes and Warburg phenotypes in cancer. Biomed Res Int 2015; 2015: 137097.
doi: 10.1155/2015/137097 DOI: https://doi.org/10.1155/2015/137097
National Comprehensive Cancer Network. Rectal Cancer (Version 3.2018). https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf
Chouchani ET, Kazak L, Spiegelman BM. Mitochondrial reactive oxygen species and adipose tissue thermogenesis: bridging physiology and mechanisms. Journal of Biological Chemistry. 2017 Oct 13;292(41):16810-6. doi: 10.1074/jbc.R117.789628 DOI: https://doi.org/10.1074/jbc.R117.789628
Tomida C, Nagano H, Yamagishi N, Uchida T, Ohno A, Hirasaka K, Nikawa T, Teshima-Kondo S. Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor. The Journal of Medical Investigation. 2017;64(3.4):262-5.
doi: 10.2152/jmi.64.262 DOI: https://doi.org/10.2152/jmi.64.262
Viel A, Bruselles A, Meccia E, Fornasarig M, Quaia M, Canzonieri V, Policicchio E, Urso ED, Agostini M, Genuardi M, Lucci-Cordisco E. A specific mutational signature associated with DNA 8-oxoguanine persistence in MUTYH-defective colorectal cancer. EBioMedicine. 2017 Jun 1;20:39-49. doi: 10.1016/j.ebiom.2017.04.022 DOI: https://doi.org/10.1016/j.ebiom.2017.04.022
Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 Sep 23;78(6):915-8.
doi: 10.1016/0092-8674(94)90266-6 DOI: https://doi.org/10.1016/0092-8674(94)90266-6
Förstermann U, Kleinert H. Nitric oxide synthase: expression and expressional control of the three isoforms. Naunyn-Schmiedeberg's archives of pharmacology. 1995 Oct 1;352(4):351-64.
doi: 10.1007/BF00172772 DOI: https://doi.org/10.1007/BF00172772
de Oliveira GA, Cheng RY, Ridnour LA, Basudhar D, Somasundaram V, McVicar DW, Monteiro HP, Wink DA. Inducible nitric oxide synthase in the carcinogenesis of gastrointestinal cancers. Antioxidants & redox signaling. 2017 Jun 20;26(18):1059-77.
doi: 10.1089/ars.2016.6850 DOI: https://doi.org/10.1089/ars.2016.6850
Said A, Raufman JP, Xie G. The role of matrix metalloproteinases in colorectal cancer. Cancers. 2014 Mar;6(1):366-75.
doi: 10.3390/cancers6010366 DOI: https://doi.org/10.3390/cancers6010366
Tauro M, Lynch C. Cutting to the chase: How matrix metalloproteinase-2 activity controls breast-cancer-to-bone metastasis. Cancers. 2018 Jun;10(6):185.
doi: 10.3390/cancers10060185 DOI: https://doi.org/10.3390/cancers10060185
Wang C, Li P, Xuan J, Zhu C, Liu J, Shan L, Du Q, Ren Y, Ye J. Cholesterol enhances colorectal cancer progression via ROS elevation and MAPK signaling pathway activation. Cellular Physiology and Biochemistry. 2017;42(2):729-42.
doi: 10.1159/000477890 DOI: https://doi.org/10.1159/000477890
Tabuso M, Homer-Vanniasinkam S, Adya R, Arasaradnam RP. Role of tissue microenvironment resident adipocytes in colon cancer. World journal of gastroenterology. 2017 Aug 28;23(32):5829.
doi: 10.3748/wjg.v23.i32.5829 DOI: https://doi.org/10.3748/wjg.v23.i32.5829
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