Tumor-associated Macrophages Promote Invasion and Metastasis of Cervical Cancer

Abstract

Objective To investigate the effect and mechanism of tumor-associated macrophages (TAMs) on the invasion and metastasis of cervical cancer. Methods Immunohistochemical method was used to detect the infiltration of TAMs in cervical lesions. The human mononuclear THP1 cell line was induced to transform into M2 type TAMs in vitro. TAMs were used to stimulate cervical cancer cells (SiHa and C33a). Scratch and Transwell assays were used to detect the effect of TAMs on the migration and invasion of cervical cancer cell lines. Western blot was used to detect the epithelial-mesenchymal transition and the expression of MMP-9 in cervical cancer cells. Results The number of TAM infiltration was positively correlated with the progression of cervical lesions. After stimulated by TAMs-CM, SiHa and C33a cells appeared interstitial-like changes, and the migration and invasion abilities were significantly enhanced (both P < 0.5). TAMs could down-regulate the expression of E-Cadherin, and up-regulate the expression of N-Cadherin, Vimentin and MMP-9. Conclusion The invasion of TAMs is closely related to the malignant transformation and progression of cervical epithelium. TAMs may promote the invasion and metastasis of cervical cancer cells by up-regulating the expression of MMP-9.

Keywords

• cervical cancer
• tumor microenvironment
• tumor-associated macrophages
• invasion
• metastasis