Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.593
Peer-review started: August 27, 2017
First decision: September 12, 2017
Revised: September 26, 2017
Accepted: November 21, 2017
Article in press: November 21, 2017
Published online: February 7, 2018
Gastric carcinoma is one of the most common malignancies and its mortality is ranked second among cancers. The tumor microenvironment plays a major role in the invasion and metastasis of gastric carcinoma. Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment. TAMs have been shown to enhance the infiltration and metastasis ability of tumor cells by expressing certain growth factors and cytokines. TAMs also suppress immune responses in the microenvironment and promote tumor progression by facilitating tumor angiogenesis and lymphangiogenesis.
Semaphorin 4D (Sema4D) is an important member of the semaphorin subfamily and plays a major role in the nervous and immune systems. Sema4D is expressed at high levels in various tumor tissues, including head and neck squamous cell carcinoma, prostate cancer, and colon cancer, and its role in promoting tumor angiogenesis is becoming a hot research topic. Sema4D is another important proangiogenic factor following vascular endothelial growth factor.
The expression of Sema4D in gastric cancer and its relationship with TAMs have not been explored. If TAMs can promote Sema4D expression and influence the characters of gastric cancer cells, this will be greatly helpful to inject new vitality into the prevention and treatment of gastric cancer.
In the present study, we explored the effect of TAMs on Sema4D expression in gastric carcinoma tissues and its role in the development and progression of gastric carcinoma to provide a new theoretical reference for the prevention and treatment of this cancer.
By using the immunohistochemical method, the expression of the TAM markers CD68 and Sema4D in gastric carcinoma and adjacent normal tissues from 290 patients and their relationships with clinical significance were analyzed. In vitro, changes of the secretory Sema4D level in SGC-7901 cells were measured using ELISA, and the effect of TAMs on SGC-7901 cell invasion and migration was assessed with invasion and migration assays, respectively.
CD68 and Sema4D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues. CD68 and Sema4D protein expression was significantly associated with histological differentiation type, TNM stage, and lymph node metastasis, and their expression levels were positively correlated with one another. In the in vitro experiment, secretory Sema4D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control. Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays. However, the mechanism by which TAMs promote gastric cancer cells to express Sema4D is not clearly now, so we should explore the signal pathway and other mechanism in the next step to make this more clearly.
In our study we found that TAMs promoted the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4D protein expression. Combined detection of TAM markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression. TAMs and Sema4D are highly expressed in many tumors and are associated with tumor development, progression, angiogenesis, invasion, and metastasis. Research on their functions and related mechanisms makes progress every day. Combined detection of CD68 and Sema4D 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.
By this study, we can learn that TAMs and Sema4D are highly expressed in gastric carcinoma and are associated with tumor development, progression, angiogenesis, invasion, and metastasis. Combined detection of CD68 and Sema4D proteins shows potential for predicting the progression trend of gastric carcinoma and determining the patient prognosis. Research on their functions and related mechanisms will make great progress in anti-tumor field. Continuous in-depth study of their mechanisms is bound to inject new vitality into the prevention and treatment of tumors.