Galectin-1-mediated expression of proteins-regulators of cell cycle and growth factors in gastric cancer

The purpose of the study was to analyze the expression of proteins-regulators of the cell cycle (p53 and p21) and receptors for endothelial (VEGFR) and epidermal (EGFR) growth factors depending on the expression of galectin-1 in tumor cells in gastric cancer.

Materials and methods. 52 patients with diagnosis of gastric cancer were examined. We used the tissue samples of malignant neoplasms of the stomach, which were obtained during surgical intervention. In tumor tissue the expression of galectin-1, p53 and p21 proteins, and receptors of VEGF and EGF were evaluated by immunohistochemistry. The obtained results were analyzed by statistical methods.

Results. It is shown that in patients with gastric cancer accompanied by overexpression of galectin-1, high expression of mutant protein p53 and EGFR in tumor tissue was recorded significantly more frequently. Low expression of VEGFR was observed in all patients with gastric cancer regardless of the level of expression of galectin-1 by tumor cells. Association of galectin-1 expression with expression of protein p53 and EGF receptor by stomach tumor cells was set.

Conclusion. The relationship between overexpression of galectin-1 and overexpression of mutant p53 protein (not showing antioncogenic properties) and receptor for epidermal growth factor (EGFR) by stomach tumor cells is a negative prognostic criterion of the neoplastic process in gastric cancer. 

1. Camby I., Le Mercier M., Lefranc F., Kiss R. Galectin-1: a small protein with major functions // Glycobiology. 2006; 16(11): 137R–157R. DOI: 10.1093/glycob/cwl025.

2. Колесник А.П. Прогностическое значение ýкспрессии р53 у больных с ранними стадиями немелкоклеточного рака легкого // Онкология. 2013; 15 (1): 20–23. Kolesnik A.P. Prognosticheskoe znachenie jekspressii r53 u bol’nyh s rannimi stadijami nemelkokletochnogo raka legkogo [Prognostic value of p53 expression in patients with early non-small cell lung cancer] // Onkologija – Oncology. 2013; 15 (1): 20–23 (in Russian).

3. Fischer C., Sanchez-Ruderisch H., Welzel M., Wiedenmann B., Sakai T., Andre S., Gabius H.-J., Khachigian L., Detjen K.M., Rosewicz S. Galectin-1 Interacts with the α5β1 Fibronectin Receptor to Restrict Carcinoma Cell Growth via Induction of p21 and p27 // The Journal of Biological Chemistry. 2005; 280 (44): 37266–37277. DOI:10.1074/jbc.m411580200.

4. Thijssen V.L., Griffioen A.W. Galectin-1 and -9 in angiogenesis: A sweet couple // Glycobiology. 2014; 24 (10): 915–920. DOI: 10.1093/glycob/cwu048.

5. Folkman J. Angiogenesis // Annual Review of Medicine. 2006; 57: 1–18. DOI:10.1146/annurev.med.57.121304. 131306.

6. 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.

7. 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 // Endocrine Related Cancer. 2010; 17(1): 7–16. DOI: 10.1677/erc-08-0304.

8. 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 // Annals of Surgical Oncology. 2008; 15(1): 69–79. DOI: 10.1245/s10434-007-9596-0.

9. He X.J., Tao H.Q., Hu Z.M., Ma Y.Y., Xu J., Wang H.J., Xia Y.J., Li L., Fei B.Y., Li Y.Q., Chen J.Z. Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin β1 // Cancer Science. 2014; 105 (11): 1402–1410. DOI: 10.1111/cas.12539.

10. Prall F., Ostwald C., Nizze H., Barten M. Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis // Applied Immunohistochemistry & Molecular Morphology. 2004; 12(2): 111–121. DOI: 10.1097/00129039-200406000-00003.

11. 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 // Oncology Letters. 2015; 10 (6): 3696 ̶3704. DOI: 10.3892/ol.2015.3747.

12. Туманский В.А., Евсеев А.В. Сравнительная оценка ýкспрессии ростовых рецепторов семейства ErbB, Кі-67 и Е-кадгерина клетками протоковой аденокарциномы поджелудочной железы // Патология. 2014; 3 (32): 55–59. Tumanskij V.A., Evseev A.V. Sravnitel’naja ocenka jekspressii rostovyh receptorov semejstva ErbB, Kі-67 i E-kadgerina kletkami protokovoj adenokarcinomy podzheludochnoj zhelezy [Comparative evaluation of expression of growth receptors of the family ErbB, Kі-67 and E-cadherin by cells of ductal pancreatic adenocarcinoma] // Patologija – Patology. 2014; 3(32): 55–59 (in Russian).

13. Гржибовский А.М. Анализ номинальных данных (независимые наблюдения) // Экология человека. 2008; 6: 58–68. Grzhibovskij A.M. Analiz nominal’nyh dannyh (nezavisimye nabljudenija) [Analysis of nominal data (independent observations)] // Jekologija cheloveka – Human Ecology. 2008; 6: 58–68 (in Russian).

14. Якушина В.Д., Васильева О.А., Рязанцева Н.В., Новицкий В.В., Савельева О.Е., Прохоренко Т.С., Старикова Е.Г., Зима А.П. Галектин-1: роль в формировании особенностей врожденного и приобретенного иммунитета // Медицинская иммунология. 2012; 14 (1– 2): 21–32. Jakushina V.D., Vasil’eva O.A., Rjazanceva N.V., Novickij V.V., Savel’eva O.E., Prohorenko T.S., Starikova E.G., Zima A.P. Galektin-1: rol’ v formirovanii osobennostej vrozhdennogo i priobretennogo immuniteta [Galectin-1: a role in the formation of features of congenital and acquired immunity] // Medicinskaja immunologija – Medical Immynology. 2012; 14 (1–2): 21–32 (in Russian).

15. Якушина В.Д., Васильева О.А., Новицкий В.В., Андреева Н.В., Старикова Е.Г., Таширева Л.А., Прохоренко Т.С., Зима А.П., Рязанцева Н.В. Влияние галектина-1 на апоптоз CD4+-лимфоцитов, дифференцированных in vitro в направлении регуляторных Т-клеток // Бюллетень экспериментальной биологии и медицины. 2013; 156(11): 616–619. Jakushina V.D., Vasil’eva O.A., Novickij V.V., Andreeva N.V., Starikova E.G., Tashireva L.A., Prohorenko T.S., Zima A.P., Rjazanceva N.V. Vlijanie galektina-1 na apoptoz CD4+-limfocitov, differencirovannyh in vitro v napravlenii reguljatornyh T-kletok [The effect of galectin-1 on apoptosis of CD4 + lymphocytes differentiated in vitro in the direction of regulatory T cells] // Bjulleten’ jeksperimental’noj biologii i mediciny – Bulletin Experimentai of Biology and Medicine. 2013; 156 (11): 616–619 (in Russian).

16. Gandhi M.K., Moll G., Smith C., Dua U., Lambley E., Ramuz O., Gill D., Marlton P., Seymour J.F., Khanna R. Galectin-1 mediated suppression of Epstein-Barr virus specific T-cell immunity in classic Hodgkin lymphoma // Blood. 2007; 110 (4): 1326–1329. DOI: 10.1182/ blood-2007-01-066100.

17. Ito K., Ralph S.J. Inhibiting galectin-1 reduces murine lung metastasis with increased CD4(+) and CD8 (+) T cells and reduced cancer cell adherence // Clinical & Experimental Metastasis. 2012; 29 (6): 561–572. DOI: 10.1007/s10585-012-9471-7.

18. Haene N.D., Sauvage S., Maris C., Adanja I., Mercier M., Decaestecker C., Baum L., Salmon I. VEGFR1 and VEGFR2 involvement in extracellular galectin-1- and galectin-3-induced angiogenesis // PLoS One. 2013; 8 (6): e67029. DOI: 10.1371/journal.pone.0067029

19. Пивень Н.В., Бураковский А.И., Прохорова В.И., Красный С.А., Шишло Л.М. Эпидермальный фактор роста и его рецепторы как перспективные клинико-диагностические и прогностические маркеры онко-патологии // Онкологический журнал. 2014; 8, 1 (29): 82–92. Piven’ N.V., Burakovskij A.I., Prohorova V.I., Krasnyj S.A., Shishlo L.M. Jepidermal’nyj faktor rosta i ego receptory kak perspektivnye kliniko-diagnosticheskie i prognosticheskie markery onkopatologii [Epidermal growth factor and its receptors as promising clinico-diagnostic and prognostic markers of oncopathology] // Onkologicheskij zhurnal – Oncological Journal. 2014; 8, 1 (29): 82–92 (in Russian).

20. Lajoie P., Goetz J.G., Dennis J.W., Nabi I.R. Lattices, rafts, and scaffolds: domain regulation of receptor signaling at the plasma membrane // Journal of Cell Biology. 2009; 185 (3): 381–385. DOI: 10.1083/jcb.200811059.