| BACKGROUND:colorectal cancer is one of the major threats to human health, the incidence andmortality rate of colorectal cancer has been at the forefront of a variety ofmalignancies.Research of mechanisms of colorectal cancer is the foundation ofovercoming this disease.Tumor microenvironment is a crucial component of cancerbiology, which is increasingly recognized as a significant factor involved in cancerinitiation, progression, metastasis, and drug resistance.It is mainly composed oftumor cells、multiple types of non-malignant cell components、a variety of solublefactors and extracellular matrix(ECM).The tumor growth is not just determined bymalignant cancer cells themselves but also by tumor microenvironment due to thegenetic and cell biological development.While the normal cellular microenvironmentcan inhibit malignant cell growth, the modifications that occur in the tumormicroenvironment synergistically support cell proliferation. Therefore,intensiveunderstanding of the contribution of tumor microenvironment to tumor progress anddevelopment is beneficial in guiding the successful design of anti-cancer therapy andnew clinical cancer diagnostics. IL-17is a inflammatory cytokine mainly secretedfrom Th17cells.FOXP3is one of the main signs of Treg,but can also be expressedby tumor cells.Both Th17cells and Treg cells are important immune cells whichform parts of the tumor microenvironment.Both Th17cells and Treg cells are subsetsof CD4+T lymphocytes CD4+T cells. Th17cells promote local inflammatoryresponse by Secretion of inflammatory cytokines such as IL-17, IL-21,IL-22,participate in the process of tumor pathological physiology. Treg cells caninhibit anti-tumor immune through various mechanisms.galectin-3is a member of β-galactoside binding protein family.galectin-3has multiple functions, and have animportant role in cancer initiation, progression and metastasis,simultaneouslyinvolved in the regulation of the immune system.And also can be secreted into thetumor microenvironment, participate in the immune system regulation through thethrough various mechanism of recruitment of macrophages and other related tumorimmune cells，but whether gelectin-3could regulate this two immune cells wasunkown.QPURPOSE AND METHODS:50cancer and matched normal tissue samples of colorectal cancer patientstreated in the Cancer Centre of Guangzhou Medical University from May,2011toDecember,2012were selected into groups,in which all the patients were treated forthe first time.The expression patterns of IL-17、FOXP3and galectin-3in CRCpatients’ tumor tissues and matched normal tissues was detected byimmunohistochemistry.We analysed the correlations beteeen clinicopathologicfactors and three protains’ expression patterns and the correlations of them.And weeventually discussed the role of three proteins in the development and progression ofcolorectal cancer.RESULTS：1. galectin-3staining was mainly localized in the nucleus and cytoplasm ofepithelial cells.In colorectal cancer tumor tissues， expression positive rate ofgalectin-3was66.0%.but in normal tissues，expression positive rate of galectin-3was12.0%.There was significant difference between them（P<0.01）.InⅠ+Ⅱ stagecolorectal cancer tumor tissues，expression positive rate of galectin-3was46.2%.butin Ⅲ+Ⅳ stage colorectal cancer tumor tissues，expression positive rate of galectin-3was87.5%.There was significant difference between them（P<0.01）. In Lymph nodemetastasis positive group,expression positive rate of galectin-3in colorectal cancertumor tissues was46.2%.but in Lymph node metastasis Negative group,expressionpositive rate of galectin-3in colorectal cancer tumor tissues was87.5%.There wassignificant difference between them（P<0.01）. 2. FOXP3staining was mainly localized in the cytoplasm and nucleus ofepithelial cells and nucleus of infiltrating immune cells.Expression positive rate ofFOXP3in stroma of the tumor group was54.0%,that of the nomal contrl group was6.0%, There was significant difference between these two groups （P<0.01）.Expression positive rate of FOXP3in stroma was associated with tumorsize,expression positive rate in the tumor diameter larger than5cm group was75.0%,but in the tumor diameter smaller than5cm group was40.0%.There wassignificant difference between these two group（sP<0.05）.Expression positive rate ofFOXP3in malignant epithelial cells was60.0%,but in the nomal epithelial cells was2.0%.There was significant difference between these two groups（P <0.01）.Therewas a negative correlation between expression of FOXP3in stroma and expressionof FOXP3in colorectal cancer cells（r=－0.508,P=0.000）.3. IL-17positive staining mainly locate in the cytoplasm of tumor infiltratingimmune cells in tumor stroma.Expression positive rate of in the tumor group was76.0%,but that of the nomal contrl group was8.0%.There was significant differencebetween these two groups（P<0.001）.4. There was a positive correlation between expression of galectin-3incolorectal cancer and expression of FOXP3in stroma（r=0.608,P=0.000）;There wasa negative correlation between expression of galectin-3in colorectal cancer andexpression of FOXP3in colorectal cancer cells（r=－0.414,P=0.003）.5. There was a positive orrelation between expression of galectin-3in colorectalcancer and expression of IL-17in stroma（r=0.289,P=0.042）.CONCLUSION:1. Expression of galectin-3in colorectal cancer was significantlyelevated,indicate that these protains play a role in the development of colorectalcancer.2. Expression of IL-17in colorectal cancer stroma was significantlyelevated.which indicate IL-17and IL-17+tumor infiltrating immune cells,such asTh17cells associated with evolution of colorectal cancer. 3. Expression of FOXP3in colorectal cancer malignant epithelial cells andstroma was significantly elevated. which indicate FOXP3and FOXP3+tumorinfiltrating immune cells,such as Treg cells play a role in the development ofcolorectal cancer.There was a negative correlation between expression of FOXP3instroma and expression of FOXP3in colorectal cancer cells,which indicated thatFOXP3expressed in colorectal cancer cells may play a role in mediating theinteraction between tumor cells and Treg cells.4. Expression of galectin-3in colorectal cancer was positively correlated withthe expression of FOXP3and IL-17in stroma,which indicated that high expressionof galectin-3in colorectal cancer may play a role in mediating the interactionbetween tumor cells and the tumor microenvironment. |
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