| Objective:Globally,gastric cancer ranks fifth in the incidence and third in the fatality of malignant tumors.In China,the incidence of gastric cancer is second only to lung cancer of male patients,,and third to breast cancer and lung cancer of female patients,on the whole,it ranks second in fatality.Gastric cancer is a slow process involving multiple factors,including infection,age,sex,diet,region,lifestyle,and so on.Many genes regulate each other and participate in many steps.So far,the molecular mechanism of its occurrence and development has not been fully explored.The abnormal complexity of its regulatory mechanism further increases the uncertainty of treatment.Therefore,it is necessary to actively explore its pathogenesis and provide specific directions for the next diagnosis and treatment.Sema4 D is a member of Semaphorin family,also known as CD100,which is a soluble protein on the cell surface.As a transmembrane protein,Sema4 D is expressed on the cell surface in the form of homologous dimer.It is highly expressed in pancreatic cancer,lung cancer,breast cancer,bladder cancer,prostate cancer,colon cancer and other malignant tumors.The expression level is positively correlated with histological grade,TNM stage and resistance to radiotherapy and chemotherapy.It plays an important role in the occurrence and development of tumors,infiltration,growth and distant metastasis.Reducing its expression can significantly inhibit the biological behavior of these malignant tumors.The occurrence and development of tumors are closely related to the internal and external environment in which tumour cells live.Tumor micro environment(TME)is the environment in which tumour cells live.TME is composed of tumor cells,cytokines,chemokines and various stromal cells.Among them,macrophages are the most frequently involved cells in the process of tumorigenesis and development.They are one of the main components of immune cell infiltration in tumor microenvironment(TME),even up to50% of the volume of tumors.The macrophages infiltrating around tumour cells are named tumor-associated macrophages(TAMs)are mainly derived from monocytes and/or microglia in peripheral blood circulation released from bone marrow.They are recruitedinto tumor tissues through the action of various cytokines and chemokines.After induction under specific conditions,macrophages can be polarized to M2(instead of activated macrophages),which can promote the invasion and migration of tumors by promoting angiogenesis,lymphangiogenesis,degradation and remodeling of extracellular matrix.Studies have shown that TAMs can affect the expression of Sema4 D,and then affect the biological behavior of colorectal cancer,liver cancer,prostate cancer and so on.However,no studies have confirmed the interaction between TAMs and Sema4 D in the occurrence and development of gastric cancer and the specific mechanism.Therefore,exploring their structure,function and mechanism of action can provide specific theoretical basis for the treatment of gastric cancer.This study summarized the role of TAMs and Sema4 D in tumors in order to provide sufficient theoretical basis for clinical diagnosis and treatment.Results:1.CD68 and Sema4 D expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues [71.7%(208/290)vs 33.8%(98/290),c2 = 83.703;74.5%(216/290)vs 42.8%(124/290),c 2 = 60.161;P < 0.01 for both];CD68 mainly infiltrated interstitial cells in gastric carcinoma tissues,Sema4 D protein expression was mainly localized in the cytoplasm and nuclei of gastric carcinoma cells and the cytoplasm of tumor interstitial cells(mainly TAMs);Positive staining for CD68 and Sema4 D was correlated with histological differentiation type,TNM stage,and lymph node metastasis(P < 0.05),but not with age,gender,or tumor size(P > 0.05);Spearman's correlation analysis revealed a positive correlation between CD68 and Sema4 D expression in gastric carcinoma tissues(r = 0.467,P < 0.01).2.Suspended human THP-1 mononuclear cells were treated with PMA,IL-4,and IL-13,and then turned into TAMs.3.TAMs enhanced the in vitro invasion and metastasis abilities of the SGC-7901 cells.4.The Elisa assay showed that the Sema4 D level in the blank control group was lower than the level in the co-culture group.Conclusions:TAMs promoted the invasion and metastasis of gastric carcinoma cells possiblythrough upregulated secretory Sema4 D protein expression.Combined detection of TAM markers,CD68 and Sema4 D,in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.TAMs and Sema4 D are highly expressed in many tumors and are associated with tumor development,progression,angiogenesis,invasion,and metastasis.Combined detection of CD68 and Sema4 D proteins shows potential for predicting the progression trend of gastric carcinoma and determining the patient prognosis.Continuous in-depth study of their mechanisms is bound to inject new vitality into the prevention and treatment of tumors. |
PDF Full Text Request