Role of galectins 1 and 3 in the recruitment of eosinophilic granulocytes into tumor tissue in gastric and colon cancers

2019 ◽  
Vol 74 (5) ◽  
pp. 317-322
Author(s):  
Yulia V. Kolobovnikova ◽  
Olga I. Urazova ◽  
Olga A. Vasilieva ◽  
Elena V. Romanova ◽  
Alexanra A. Komar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Eosinophilic Infiltration ◽  
Tissue Eosinophilia ◽  
Eosinophilic Granulocytes ◽  
Galectin 3 ◽  
Blood Eosinophils ◽  
Low Expression ◽  
Gene Mrna

Background: Gastric and colon tumors are often associated with eosinophilic infiltration of tumor tissue, the significance of which is still not entirely clear. The recruitment of eosinophils into the tissues can be in part regulated by galectins ― galactose-binding proteins which are expressed by a variety of tissues and are capable of exerting a broad range of effects. Aims: To evaluate the expression of galectin-1 and galectin-3 in tumor tissue, and gal-3 gene mRNA expression in blood eosinophils in patients with gastric and colon cancer with or without tissue eosinophilia. Materials and methods: The study included a total of 107 patients (84 males and 23 females, average age 60,9 6,8) with verified gastric cancer (52 persons) and colon cancer (55 persons), who underwent treatment or were registered at the dispensary at the regional medical institution Tomsk Regional Oncology Center (Tomsk, Russia). The control group consisted of 15 men and 11 women of comparable age. The materials of the research included samples of gastric and colon tumors obtained during surgery, and eosinophilic granulocytes isolated from whole blood by immunomagnetic separation. Galectin-1 and galectin-3 expression in tumor tissue was evaluated by immunohistochemistry. The expression of gal-3 gene mRNA in eosinophils was determined by real-time reverse transcription polymerase chain reaction. Statistical analysis of the results was carried out using the non-parametric Mann-Whitney U test for independent samples with Benjamini-Hochberg procedure for multiple comparisons, and the Chi-square Pearson criterion with Yates correction. Results: In patients with gastric cancer and colon cancer, regardless of the presence of tissue eosinophilia, low expression of galectin-3 in the tumor tissue and high expression of gal-3 gene mRNA in peripheral blood eosinophils were found. Gastric and colon cancer patients with eosinophilic infiltration of tumor tissue were characterized by low expression of galectin-1 within tumor cells (in 64.0% cases, 2 = 4.890, р = 0.029; and in 73.9% cases, 2 = 5.981, p = 0.031 respectively). There was a statistically significant connection between the level of galectin-1 expression by tumor cells and the presence of tissue eosinophilia both in gastric ( = 0.307) and colon cancer ( = 0.330). Conclusion: Low expression of galectin 1 and 3 by tumor cells in gastric and colon cancer with tissue eosinophilia indicates the lack of a significant effect of these proteins on the process of recruiting eosinophilic granulocytes into tumor tissue. Increased expression of galectin-3 in blood eosinophils in gastric and colon cancer is not associated with the presence of eosinophilic infiltration of tumor tissue.

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

2019 ◽  
Vol 18 (1) ◽  
pp. 211-219
Author(s):  
Yu. V. Kolobovnikova ◽  
K. I. Yankovich ◽  
E. V. Romanova ◽  
A. I. Dmitrieva ◽  
O. I. Urazova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Colon Cancer ◽  
Growth Factor ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Malignant Tumors ◽  
Tissue Eosinophilia ◽  
Eosinophilic Granulocytes ◽  
Blood Eosinophils

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.

scholarly journals The expression of CCL11/eotaxin, CCR3 receptor and eosinophil peroxidase in tumor tissue in gastric and colon cancers

2018 ◽  
Vol 17 (3) ◽  
pp. 80-87 ◽  
Author(s):  
Yu. V. Kolobovnikova ◽  
K. I. Yankovich ◽  
E. V. Romanova ◽  
A. I. Dmitrieva ◽  
V. V. Novitskiy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Immunohistochemical Method ◽  
Eosinophilic Infiltration ◽  
Marker Enzyme ◽  
Tissue Eosinophilia ◽  
Colon Cancers ◽  
Eosinophil Peroxidase ◽  
Eosinophilic Granulocytes

The purpose of the study was to analyze the expression of CCL11/eotaxin, CCR3 receptor to eotaxin and eosinophil peroxidase (EXP) in tumor tissue and its relation to tissue eosinophilia in gastric and colon cancers.Materials and methods. 52 patients with gastric cancer and 55 patients with colon cancer were examined. The material of the study was samples of malignant tumors of the stomach and large intestine obtained during a surgery. The expression of CCL11/eotaxin, CCR3 and EXP in the tumor tissue was evaluated by immunohistochemical method. For statistical processing of the results, one-factor dispersion and correlationregression (by Spearman) methods of analysis were used.Results. High expression of CCL11/eotaxin by tumor cells is typical of stomach and colon cancers with eosinophilic infiltration of the tumor tissue. The CCR3 receptor to eotaxin on the cell membrane of infiltration of the tumor tissue in gastric and colon cancers is found in 100% of cases. Expression of CCR3 (at stomach cancer) and EXP (at stomach and colon cancers) by cells of the tumor microenvironment with eosinophilic granulocytes infiltration is significantly higher than in the cells of the tumor microenvironment without eosinophilic infiltration.Conclusion. Tissue eosinophilia in gastric and colon cancers develops due to the ability of transformed malignant cells to produce CCL11/eotaxin that mediates the attraction of CCR3-expressing eosinophil granulocytes in the tumor tissue. High level of EPX (marker enzyme of eosinophils) expression by cells of tumor microenvironment in the gastric and colon cancers with tissue eosinophilia suggests the expressed cytotoxic potential of eosinophilic granulocytes, which can be directed against tumor cells.

scholarly journals Endogenous and exogenous galectin-3 promote the adhesion of tumor cells with low expression of MUC1 to HUVECs through upregulation of N-cadherin and CD44

2018 ◽  
Vol 98 (12) ◽  
pp. 1642-1656 ◽  
Author(s):  
Zhanqi Cao ◽  
Zhaojun Hao ◽  
Ming Xin ◽  
Lugang Yu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Galectin 3 ◽  
Low Expression

The formation mechanisms of tumor-associated tissue eosinophilia in gastric cancer and colon cancer

2017 ◽  
pp. 74-80
Author(s):  
В.В. Новицкий ◽  
К.И. Янкович ◽  
Ю.В. Колобовникова ◽  
А.И. Дмитриева ◽  
О.И. Уразова ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Colon Cancer ◽  
Tumor Tissue ◽  
Molecular Genetic ◽  
Formation Mechanisms ◽  
Tissue Samples ◽  
Tissue Eosinophilia ◽  
Neoplastic Lesion ◽  
Key Factor ◽  
Mechanisms Of Formation

Опухолеассоциированная тканевая эозинофилия определяется как эозинофильная инфильтрация стромы опухоли. Эта реакция, как полагают, играет важную роль в канцерогенезе. Считается, что эозинофилы обладают противоопухолевой активностью за счет высвобождения цитотоксических белков. Цель исследования - изучение молекулярно-генетических механизмов формирования опухолеассоциированной тканевой эозинофилии у больных раком желудка и толстой кишки. Методика. Материалом исследования служили образцы опухолевой ткани пациентов с диагнозом рак желудка или толстой кишки . Подсчитывали количество эозинофилов, инфильтрирующих опухолевую ткань, а также оценивали экспрессию эотаксина-1 (ключевого фактора хемотаксиса эозинофилов) и его рецептора CCR3 в опухолевой ткани методом иммуногистохимии. Было изучено распределение полиморфных вариантов генов CCL11 (А384G) , CCR3 (T51С) , IL5 (С703Т) и IL5R (G80А) . Геномную ДНК выделяли из образцов опухолевой ткани. Генотипирование образцов ДНК по полиморфизмам генов осуществляли путем ПДРФ-анализа продуктов ПЦР-амплификации специфических участков генома с последующей визуализацией в ультрафиолетовом свете. Результаты. Показана более высокая экспрессия эотаксина-1 и CCR3 в ткани опухоли при раке желудка и толстой кишки, ассоциированном с эозинофилией. Установлена ассоциация эозинофильной инфильтрации опухолевой ткани с носительством генотипа СС и аллеля С полиморфизма T51С гена CCR3 и генотипа СС и аллеля С полиморфизма С703Т гена IL5 . Заключение. Формирование опухолеассоциированной тканевой эозинофилии при раке желудка и толстой кишки опосредованно действием эотаксина-1 и его рецептора. Результаты молекулярно-генетического исследования указывают на генетически детерминированный характер эозинофилии при раке желудка и толстой кишки. Tumor-associated tissue eosinophilia is defined as eosinophilic stromal infiltration of a tumor. Tumor-associated tissue eosinophilia is believed to play a significant role in carcinogenesis. It is believed that eosinophils have antitumor activity due to the release of cytotoxic proteins. The aim of this study was to investigate the molecular-genetic mechanisms of formation of tumor-associated tissue eosinophilia in patients with gastric cancer and colon cancer. Methods. Tumor tissue samples from patients with gastric cancer and colon cancer were reviewed. We counted the number of infiltrating eosinophils in neoplastic lesion tissue and we evaluated the expression of eotaxin-1 (a key factor of chemotaxis of eosinophils) and its receptor CCR3 in tumor tissue by immunohistochemical staining. The distribution of polymorphic variants of genes CCL11 (А384G), CCR3 (Т51С), IL5 (С703Т) and of the IL5R (G80А) was studied. DNA was isolated from tumor tissue samples. Genotyping of polymorphisms was carried out by polymerase chain reaction (PCR), followed by digestion with the appropriate restriction enzyme (PCR-RFLP) and agarose-gel electrophoresis. Results. It is shown that higher expression eotaxin-1 and CCR3 is determined in the tumor tissue of gastric cancer and colon cancer associated with eosinophilia. It is established that eosinophilic infiltration of the tumor tissue is associated with the carriers of CC genotype and C allele of the gene CCR3 (Т51С) and CC genotype and C allele of gene IL5 (С703Т) . Conclusion. The formation of tumor-associated tissue eosinophilia in gastric cancer and colon cancer is mediated through the action eotaxin-1 and its receptor. The results of molecular-genetic studies indicate a genetically determined character of eosinophilia in gastric cancer and colon cancer.

scholarly journals Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Atsuhito Uneda ◽  
Kazuhiko Kurozumi ◽  
Atsushi Fujimura ◽  
Kentaro Fujii ◽  
Joji Ishida ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
In Silico ◽  
Tumor Tissue ◽  
The Cancer Genome Atlas ◽  
Macrophage Infiltration ◽  
Macrophage Migration

AbstractGlioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells.

Concurrent measurements of carcinoembryonic antigen, glucosephosphate isomerase, gamma-glutamyltransferase, and lactate dehydrogenase in malignant, normal adult, and fetal colon tissues.

1980 ◽  
Vol 26 (13) ◽  
pp. 1809-1812 ◽  
Author(s):  
D D Munjal
Keyword(s):  
Colon Cancer ◽  
Lactate Dehydrogenase ◽  
Carcinoembryonic Antigen ◽  
Tumor Tissue ◽  
Human Colon ◽  
Normal Adult ◽  
Metastatic Colon Cancer ◽  
Glucosephosphate Isomerase ◽  
Adult Human ◽  
Fetal Organs

Abstract Carcinoembryonic antigen and activities of glucosephosphate isomerase (EC 5.3.1.9), γ-glutamyltransferase (EC 2.3.2.2), and lactate dehydrogenase (EC 1.1.1.27) were measured in aqueous extracts of fetal, normal adult, and malignant human colon tissues. Fetal colon, as well as primary and metastatic colon tumor tissue, showed higher activities of these analytes than did normal adult human colon. Liver metastases of colon cancer gave the highest values, normal adult human colon the lowest. Statistically, these differences were more striking in the case of carcinoembryonic antigen and glucosephosphate isomerase than for γ-glutamyltransferase or lactate dehydrogenase. In contrast to the other markers, γ-glutamyltransferase activity was lower in fetal organs than in normal adult colon and colon tumors. These results are consistent with earlier observations that activities of these markers are significantly increased in the blood of patients with metastatic colon cancer.

Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening

2021 ◽  
pp. 1-9
Author(s):  
Thais Sobanski ◽  
Lidia Maria Rebolho Batista Arantes ◽  
Wellington dos Santos ◽  
Marcus Matsushita ◽  
Marco Antonio de Oliveira ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Tissue ◽  
Methylation Profile ◽  
Precursor Lesions ◽  
Cancer Genes

scholarly journals Downregulated KIF3B Induced by miR-605-3p Inhibits the Progression of Colon Cancer via Inactivating Wnt/β-Catenin

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qilong Wang ◽  
Xiaomin Hao ◽  
Gang Xu ◽  
Tiesheng Lv
Keyword(s):  
Colon Cancer ◽  
Tumor Cells ◽  
Malignant Disease ◽  
Luciferase Reporter ◽  
High Morbidity ◽  
Transwell Assay ◽  
Flow Cytometry Assay ◽  
Colon Cells ◽  
Proliferation And Invasion ◽  
Dual Luciferase Reporter Assay

Colon cancer is a common malignant disease with high morbidity and mortality, and miRNA dysfunction has been confirmed as an important reason for cancer development. Several studies have verified miR-605-3p as a tumor inhibitor while its roles in colon cancer remain uncertain. In this study, the specimen of the patients and the cell lines of colon cancer were used to observe the expression of miR-605-3p, and the CCK-8, Transwell assay, and flow cytometry assay were used to observe the functions of miR-605-3p in colon cancer cells. The downstream factors of miR-605-3p were predicted by TargetScan and then were verified by dual-luciferase reporter assay. Moreover, western blot was used to investigate the effect of miR-605-3p on Wnt/β-catenin signal pathway. The result showed that miR-605-3p was extremely downregulated in the pathological tissues and tumor cells, and miR-605-3p could effectively induce the apoptosis and impede the proliferation and invasion of the tumor cells. It was found that KIF3B was a target of KIF3B; decreased KIF3B could reverse the effects of miR-605-3p on colon cancer. Besides, the inactivated Wnt/β-catenin pathway was also observed in colon cells when miR-605-3p was upregulated, and the phenomenon could be rescued by KIF3B upregulation. In conclusion, miR-605-3p could inactivate the Wnt/β-catenin pathway induced via promoting KIF3B expression.

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