A.V. Kurnosenko1, G.V. Reinhardt2, V.S. Poletika3, Yu.V. Kolobovnikova4, A.I. Dmitrieva5, M.Yu. Grishchenko6, V.K. Abramov7, O.I. Urazova8

1–4, 6–8 Federal State Budgetary Educational Institution of Higher Education «Siberian State Medical University» of the Ministry of Health of Russia (Tomsk, Russia)

1,5 Regional State Autonomous Healthcare Institution «Tomsk Regional Oncology Center» (Tomsk, Russia)

8 urazova72@yandex.ru

An important role in the pathogenesis of colorectal cancer (CRC) belongs to the growth factors VEGF (vascular endothelial growth factor) and EGF (epidermal growth factor), which, through interaction with specific receptors, induce the proliferation of transformed (tumor) cells. Beta-galactoside-binding proteins, galectins 1 and 3, can exhibit synergism in relation to growth factors, performing similar functions both independently and through inducing the secretion of VEGF and EGF and the expression of their cognate receptors. In general, the mechanism of mutual influence of the above-mentioned factors in the pathogenesis of CRC has not been studied. The purpose of the research is to investigate the relationship between plasma and tumor galectins 1 and 3 with the content of endothelial (VEGF) and epidermal (EGF) growth factors in peripheral blood and the expression of VEGFR and EGFR receptors in tumor tissue in patients with colorectal cancer. In patients with cancer, an increase in the concentration of VEGF in the peripheral blood was found compared with the group of healthy donors, while the plasma level of EGF (in patients with cancer and healthy donors) and the relative content of tumor VEGF+ - and EGF+ cells (in patients with cancer and colon adenomas) were comparable. A direct correlation has been discovered between the content of growth factor VEGF and galectins (types 1 and 3) in the peripheral blood of patients with CRC. High plasma concentration of EGF is associated with the percentage of tumor galectin-3+ cells, and intratumoral EGFR expression is associated with overexpression of galectin-1 in CRC. Thus, in CRC, there is an increased concentration of circulating VEGF, which is associated with increased levels of galectin-1 and galectin-3 in the peripheral blood. The direct relationship between the content of EGF in the blood plasma and the number of tumor galectin-3-positive tumor cells, as well as between the number of EGFR- and galectin-1-positive tumor cells in patients with colorectal cancer reflects the ability of galectins (types 1 and 3) to modulate VEGF- and EGF-mediated interaction between tumor cells and their microenvironment. The involvement of galectins 1 and 3 in the mechanisms of VEGF- and EGF-dependent tumor progression in colorectal cancer remains a subject of ongoing research.

1. Vallis J., Wang P.P. The Role of Diet and Lifestyle in Colorectal Cancer Incidence and Survival. In: Morgado-Diaz J.A., editor. Gastrointestinal Cancers. Brisbane (AU): Exon Publications. 2022. P. 13–24. DOI: https://doi.org/10.36255/exon-publications-gastrointestinal-cancers-diet-colorectal-cancer
2. Sostoyaniye onkologicheskoy pomoshchi naseleniyu Rossii v 2021 godu. pod red. A.D. Kaprina. V.V. Starinskogo. A.O. Shakhzadovoy. M.: MNIOI im. P.A. Gertsena – filial FGBU «NMITs radiologii» Minzdrava Rossii. 2022. 239 s. (in Russian).
3. Chekhonin V.P., Shein S.A., Korchagina A.A., Gurina O.I. Rol VEGF v razvitii neoplasticheskogo angiogeneza. Vestnik Rossiy-skoy akademii meditsinskikh nauk. 2012. № 2. S. 23–34. (in Russian).
4. Chekhonin V., Shein S, Korchagina A, Gurina O. VEGF in tumor progression and targeted therapy. Current Cancer Drug Targets. 2013. V. 13. Is. 4. P. 423–443. DOI: 10.2174/15680096113139990074
5. Siveen K., Prabhu K., Krishnankutty R., Kuttikrishanin S., Tsalou M. Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges. Current Vascular Pharmacology. 2017. V. 15. № 4. P. 339–351. DOI: 10.2174/1570161115666170105124038
6. Barrow H., Rhodes J. M., Yu L.-G. The role of galectins in colorectal cancer progression. International Journal of Cancer. 2011. V. 129. № 1. P. 1–8. DOI: 10.1002/ijc.25945
7. Kim S.-J., Chun K.-H. Non-classical role of Galectin-3 in cancer progression: translocation to nucleus by carbohydrate-recognition independent manner. BMB reports. 2020. V. 53. № 4. P. 173–180. DOI: 10.5483/BMBRep.2020.53.4.020
8. Li S., Pritchard D. M., Yu L.-G. Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells. Cell Death & Disease. 2023. V. 14. № 4. P. 268. DOI: 10.1038/s41419-023-05789-x
9. Song L., Tang J., Owusu L., Sun M.-Zh., Wu J., Zhang J. Galectin-3 in cancer. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2014. V. 431. P. 185–191. DOI: 10.1016/j.cca.2014.01.019
10. Huang Y., Wang H.-Ch., Zhao J., Wu M.-H., Shih Ts.-Ch. Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment. Biomolecules. 2021. V. 11. № 10. P. 1398. DOI:10.3390/biom11101398
11. Martínez-Bosch N., Navarro P. Galectins in the Tumor Microenvironment: Focus on Galectin-1. Advances in Experimental Medicine and Biology. 2020. V. 1259. P. 17–38. DOI: 10.1007/978-3-030-43093-1_2
12. Wang C., Ma L., Zhuang Y., Wei Yu. Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis. Pathology - Research and Practice. 2019. V. 215. № 10. P. 152612. DOI: 10.1016/j.prp.2019.152612
13. Kolobovnikova Yu.V., Urazova O.I., Poletika V.S., Reyngardt G.V., Romanova E.V., Kurnosenko A.V., Dmitriyeva A.I., Yankovich K.I., Grishchenko M.Yu. Galektin-1.3-zavisimyye faktory patogeneza dizregulyatsii adaptivnogo immuniteta pri rake tolstogo kishechnika. Klinicheskaya patofiziologiya. 2021. T. 27. № 3. S. 69–74. (in Russian).
14. Vasilyeva O.A., Prokhorenko T.S., Kolobovnikova Yu.V., Poletika V.S., Urazova O.I., Kononova T.E., Churina E.G., Reyngardt G.V., Kurnosenko A.V. Galektin-3 kak modulyator tsitokinoposredovannoy kooperatsii limfotsitov in vitro. Tsitokiny i vospa-leniye. 2022. № 3-4. S. 21–27. (in Russian).
15. Stillman B. N., Hsu D. K., Pang M. et al. Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J. Immunol. 2006. V. 176. № 2. P. 778–789. DOI: 10.4049/jimmunol.176.2.778
16. Chen Y.-F. Wang Ch.-Ch., Hsu Ch.-Y., Huang E.-Y. Involvement of Galectin-1 Tumor Microenvironment in Radiosensitivity. Anticancer Research. 2021. V. 41. № 5. Р. 2321–2331. DOI: 10.21873/anticanres.15007
17. Svetozarskiy N.L., Artifeksova A.A., Svetozarskiy S.N. Faktor rosta endoteliya sosudov: biologicheskiye svoystva i prakti-cheskoye znacheniye (obzor literatury). Journal of Siberian Medical Sciences. 2015. № 5. URL: https://cyberleninka.ru/article/n/faktor-rosta-endoteliya-sosudov-biologicheskie-svoystva-i-prakticheskoe-znachenie-obzor-literatury (data obrashcheniya: 30.01.2024). (in Russian).
18. Chou F.-C., Chen H.-Y., Kuo Ch.-Ch., Sutwu H.-K. Role of Galectins in Tumors and in Clinical Immunotherapy. International Journal of Molecular Sciences. 2018. V. 19. № 2. P. 430. DOI: 10.3390/ijms19020430
19. Kushlinskiy N.E., Kovaleva O.V., Prishchep P.L., Zybina N.N., Yurishich V., Alferov A.A., Kuzmin Yu.B., Goryacheva I.O., Kuznetsov I.N., Bulycheva I.V., Varfolomeyeva S.R., Sushentsov E.A., Gershteyn E.S., Rogozhin D.V., Yanushevich O.O., Stilidi I.S. Galektin-3 v syvorotke krovi bolnykh opukholyami kostey. Byulleten sibirskoy meditsiny. 2023. T. 22. № 2. S. 68–77. DOI: 10.20538/1682-0363-2023-2-68-77 (in Russian).
20. Markowska A.I., Jefferies K.C., Panjwani N. Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells. The Journal of Biological Chemistry. 2011. V. 286. № 34. P. 29913–29921. DOI: 10.1074/jbc.M111.226423
21. Wu K.-L., Kuo Ch.-M., Huang E.-Yu., Pan H.-M., Huang Ch.-Ch. Extracellular galectin-3 facilitates colon cancer cell migration and is related to the epidermal growth factor receptor. American Journal of Translational Research. 2018. V. 10. № 8. P. 2402–2412.