Preview

Bulletin of Siberian Medicine

Advanced search

VEGF-and EGF-mediated cooperation of eosinophilic granulocytes and tumor cells in gastric and colon cancer

https://doi.org/10.20538/1682-0363-2019-1-211-219

Abstract

Aim of the research – to analyze secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by blood eosinophilic granulocytes in vitro, together with an expression of VEGFR and EGFR in tumor tissue in gastric and colon cancer in association with tissue eosinophilia.

Materials and methods. A total of 52 patients with gastric cancer and 50 patients with colon cancer were examined. The material of the research included supernatants of eosinophil cultures and samples of malignant tumors tissues of the stomach and colon. Enzyme-linked immunosorbent assay was used to determine the contents of VEGF and EGF in the eosinophil culture supernatants in vitro. The expression of VEGFR and EGFR in tumor tissue was evaluated by immunohistochemistry. The results were analyzed by statistical methods.

Results. An increase in basal and r-IL-5-induced secretion of VEGF by eosinophilic granulocytes of blood in vitro was found in patients with gastric cancer accompanied by tissue eosinophilia. The concentration of EGF in the culture of blood eosinophils in vitro with the addition of r-IL-5 increased in patients with eosinophilic infiltration of tumor tissue, regardless of the localization of the pathological process,both in patients with gastric cancer and colon cancer. Eosinophilic infiltration of the tumor tissue in gastric cancer and colon cancer was combined with hypo-expression of EGFR by tumor cells; VEGFR receptor expression was not dependent on the presence of eosinophilic granulocytes in the tissue of tumors.

Conclusion. Hypersecretion of vascular endothelial growth factor VEGF and epidermal growth factor EGF (upon stimulation with r-IL-5) by blood eosinophils in vitro in patients with gastric and colon cancer with tissue eosinophilia indicates an increase in the activity of these cells. Deficiency of expression of VEGF and EGFR receptors in tumor tissue causes violation of cooperative interaction of eosinophilic granulocytes and tumor cells in malignant tumors of the stomach and large intestine.

About the Authors

Yu. V. Kolobovnikova
Siberian State Medical University (SSMU)
Russian Federation

Kolobovnikova Yuliya V., DM, Professor, Pathophysiology Division

2, Mosсow Trakt, Tomsk, 634055



K. I. Yankovich
Siberian State Medical University (SSMU); Tomsk Regional Oncological Dispensary (TROD)
Russian Federation

Yankovich Kristina I., Junior Researcher, Central Research Laboratory, SSMU; Doctor, Clinical Diagnostic Laboratory, TROD

2, Mosсow Trakt, Tomsk, 634055, 

115, Lenin Av., Tomsk, 634050



E. V. Romanova
Siberian State Medical University (SSMU)
Russian Federation

Romanova Elena V., Senior Lecturer, Microbiology and Virology Division

2, Mosсow Trakt, Tomsk, 634055



A. I. Dmitrieva
Tomsk Regional Oncological Dispensary (TROD)
Russian Federation

Dmitrieva Аlla I., DM, Head of Clinical Diagnostic Laboratory

115, Lenin Av., Tomsk, 634050



O. I. Urazova
Siberian State Medical University (SSMU); Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Russian Federation

Urazova Olga I., DM, Professor, Corresponding Member of RAS, Head of the Pathophysiology Division, SSMU; Professor of the Department of Complex Information Security of Computer Systems, TUSUR

2, Mosсow Trakt, Tomsk, 634055, 

40, Lenin Av., Tomsk, 634050



V. V. Novitskii
Siberian State Medical University (SSMU); Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Russian Federation

Novitskii Vyacheslav V., DM, Professor, Academician of RAS, Honored Scientist of Russia, Professor, Pathophysiology Division, SSMU; Professor, Department of Complex Information Security of Computer Systems, TUSUR

2, Mosсow Trakt, Tomsk, 634055, 

40, Lenin Av., Tomsk, 634050



V. S. Poletika
Siberian State Medical University (SSMU)
Russian Federation

Poletika Vadim S., PhD Student, Pathophysiology Division

2, Mosсow Trakt, Tomsk, 634055



References

1. Quail D.F., Joyce J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013; 19 (11): 1423–1437. DOI: 10.1038/nm.3394.

2. Wei Y., Zhang X., Wang G., Zhou Y., Luo M., Wang S., Hong C. The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage I-III colorectal cancer. Asia-Pacific Journal of Clinical Oncology. 2018; Oct. 14 (5): 243–251. DOI: 10.1111/ajco.12871.

3. Legrand F., Driss V., Delbeke M., Loiseau S., Hermann E., Dombrowicz D., Capron M. Human eosinophils exert TNF-α and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. The Journal of Immunology. 2010; 185 (12): 7443–7451. DOI: 10.4049/jimmunol.1000446.

4. Reichman H., Karo-Atar D., Munitz A. Emerging roles for eosinophils in the tumor microenvironment. Trends in Cancer. 2016; 2 (11): 664–675. DOI: 10.1016/j.trecan.10.002.

5. Kolobovnikova Yu.V., Yankovich K.I., Romanova E.V., Dmitrieva A.I., Noviczkij V.V., Urazova O.I. The expression of CCL11/ eotaxin, CCR3 receptor and eosinophil peroxidase in tumor tissue in gastric and colon cancers. Bulletin of Siberian Мedicine. 2018; 17 (3): 80–87 (in Russ.). DOI: 10.20538/1682-0363-2018-3-80-87.

6. Legrand F., Driss V., Woerly G. Loiseau S., Hermann E., Fournie J.J., Heliot L., Mattot V., Soncin F., Gougeon M.L., Dombrowicz D., Capron M. A functional γδTCR/ CD3 complex distinct from γδT cells is expressed by human eosinophils. PLoS One. 2009; 4 (6). DOI: 10.1371/journal.pone.0005926. URL: http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005926&-type=printable.

7. Puxeddu I., Alian A., Piliponsky A.M., Ribatti D., Panet A., Levi-Schaffer F. Human peripheral blood eosinophils induce angiogenesis. Int. J. Biochem. Cell Biol. 2005; 37 (3): 628–636. DOI: 10.1016/j.biocel.2004.09.001.

8. Miller S.S., Apostolopoulos V., Nurgali K. Eosinophils in сancer: favourable or unfavourable? Curr. Med. Chem. 2016; 23 (7): 650–666.

9. Folkman J. Angiogenesis. Annu. Rev. Med. 2006; 57: 1–18.

10. Tiash S., Chowdhury E.H. Growth factor receptors: promising drug targets in cancer. J. Cancer Metastasis Treat. 2015; 1: 190–200. DOI: 10.4103/2394-4722.163151.

11. Rapisarda A., Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv. Cancer Res. 2012; 114: 237–267. DOI: 10.1016/B978-0-12-386503-8.00006-5.

12. Manual of immunohistochemical methods in diagnosis of human tumors; ed. S.V. Petrov, N.T. Rayhlin. 3th issue, Kazan: Titul Publ., 2004: 456 (in Russ.).

13. Tumanskiy V.A., Evseev A.V. Comparative evaluation of growth factors ErbB, Кі-67 and Е-cadherin expression in cells of pancreatic adenocarcinoma. Pathology. 2014; 3 (32): (in Russ.).

14. Niyaz M., Anwer J., Liu H. Zhang L., Shayhedin I., Awut I. Characterization of the expression and clinical features of epidermal growth factor receptor and vascular endothelial growth factor receptor 2 in esophageal carcinoma. Oncol. Lett. 2015; 10 (6): 3696–3704. DOI: 10.3892/ol.2015.3747.

15. Ciardiello F., Troiani T., Bianco R., Orditura M., Morgillo F., Martinelli E., Morelli M.P., Cascone T., Tortora G. Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy. Ann. Oncol. 2006; 17 (7): 109–114. DOI: 10.1093/annonc/mdl962.

16. Niu G., Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Current Drug Targets. 2010; 11 (8): 1000–1017.

17. Rosenberg H.F., Dyer K.D., Foster P.S. Eosinophils: changing perspectives in health and disease. Nat. Rev. Immunol. 2013; 13 (1): 9–22. DOI: 10.1038/nri3341.

18. Shamri, R., Xenakis J.J., Spencer L.A. Eosinophils in innate immunity: an evolving story. J. Cell and Tissue Research. 2010; 343 (1): 57–83. DOI: 10.1007/s00441-010-1049-6.

19. Lee S.H., Jeong D., Han Y.S., Baek M.J. Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis. Annals of Surgical Treatment and Research. 2015; 89 (1): 1–8. DOI: 10.4174/astr.2015.89.1.1.

20. Wang K., Peng H.L., Li L.K. Prognostic value of vascular endothelial growth factor expression in patients with prostate cancer: a systematic review with meta-analysis. Asian Pacific Journal of Cancer Prevention. 2012; 13 (11): 5665–5669. DOI: 10.7314/APJCP.2012.13.11.5665.

21. Rodriguez-Antona C., Pallares J., Montero-Conde C., Inglada-Perez L., Castelblanco E., Landa I., Leskela S., Leandro-Garcia L. J., Lopez-Jimenez E., Leton R., Cascon A., Lerma E., Martin M.C., Carralero M.C., Mauricio D., Cigudosa J.C., Matias-Guiu X., Robledo M. Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis. Endocr. Relat. Cancer. 2010; 17 (1): 7–16. DOI: 10.1677/ERC-08-0304.

22. Pallares J., Rojo F., Iriarte J., Morote J., Armadans L.I., de Torres I. Study of microvessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues. Histol. Histopathol. 2006; 21 (8): 857–865. DOI: 10.14670/HH-21.857.

23. Carmeliet P., Jain R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011; 473 (7347): 298–307. DOI: 10.1038/nature10144.

24. Rafii S., Lyden D., Benezra R., Hattori K., Heissig B. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat. Rev. Cancer. 2002; 2 (11): 826–835. DOI: 10.1038/nrc925.

25. Piven’ N.V., Burakovskiy A.I., Prohorova V.I., Krasniy S.A., Shishlo L.M. Epidermal growth factor and its receptors as perspective clinical-diagnostic and prognostic markers of oncopathology. Journal of Oncology. 2014; 1 (29): 82–92 (in Russ.).

26. Normanno N., De Luca A., Bianco C., Strizzi L., Mancino M., Maiello M.R., Carotenuto A., De Feo G., Caponigro F., Salomon D.S. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006; 366 (1): 2–16. DOI: 10.1016/j.gene.2005.10.018.

27. Mendelsohn J., Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J. Clin. Oncol. 2003; 21 (14): 2787–2799. DOI: 10.1200/JCO.2003.01.504.

28. Lieto E., Ferraraccio F., Orditura M., Castellano P., Mura A.L., Pinto M., Zamboli A., De Vita F., Galizia G. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann. Surg. Oncol. 2008; 15 (1): 69–79. DOI: 10.1245/s10434-007-9596-0.

29. Niyaz M., Anwer J., Liu H., Zhang L., Shayhedin I., Awut I. Characterization of the expression and clinical features of epidermal growth factor receptor and vascular endothelial growth factor receptor 2 in esophageal carcinoma. Oncol. Lett. 2015; 10 (6): 3696–3704. DOI: 10.3892/ol.2015.3747.

30. Galizia G., Lieto E., Ferraraccio F., De Vita F., Castellano P., Orditura M., Imperatore V., La Mura A., La Manna G., Pinto M., Catalano G., Pignatelli C., Ciardiello F. Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann. Surg. Oncol. 2006; 13 (6): 823– 835. DOI: 10.1245/ASO.2006.05.052.


Review

For citations:


Kolobovnikova Yu.V., Yankovich K.I., Romanova E.V., Dmitrieva A.I., Urazova O.I., Novitskii V.V., Poletika V.S. VEGF-and EGF-mediated cooperation of eosinophilic granulocytes and tumor cells in gastric and colon cancer. Bulletin of Siberian Medicine. 2019;18(1):211-219. https://doi.org/10.20538/1682-0363-2019-1-211-219

Views: 933


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)