Infiltrated M2 tumour-associated macrophages in the stroma promote metastasis and poor survival in oesophageal squamous cell carcinoma
Jian Zhou1,3,4*, Shutao Zheng2,3*, Tao Liu2,3, Qing Liu2,3, Yumei Chen1,2, Rong Ma1,2, Doudou Tan1,3 and Xiaomei Lu1,3
1Tumor Hospital Affiliated to Xinjiang Medical University, 2Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 3State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Uygur Autonomous Region, Urumqi and 4Department of Pathology, the Affiliated Hospital of Southwest Medical University, Luzhou, PR China
*Contributed equally
Offprint requests to: Dr. Xiaomei Lu, Tumor Hospital Affiliated to Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Inicidence Dieases, Urumqi 830000, Xinjiang Uygur Autonomous Region, PR China. e-mail: luxiaomei88@163.com
Summary. Although M2 tumour-associated macrophages (M2 TAMs) have been shown to be associated with the progression and metastasis of breast cancer, their role in oesophageal squamous cell carcinoma (ESCC) remains less well understood. Therefore, to understand the clinicopathological significance of infiltrated M2 TAMs in ESCC, statistical analysis was performed after immunohistochemical evaluation of CD163 expression, a well-accepted surface marker of M2 TAMs in ESCC. To gain insight into the effect of M2 TAMs, ESCC cell lines Eca109 and KYSE150 cells were co-cultured with M2 TAMs artificially induced from THP-1 cells. The variations in the proliferation, migration and invasion were assessed using the MTT, wound-healing and Transwell assays, respectively. The variation in the typical biomarkers of the epithelial-mesenchymal transition (EMT) was evaluated using western blotting. Infiltrated M2 TAMs were confirmed to predominate in the stroma of ESCC relative to normal controls. Moreover, it turned out that M2 TAMs were shown to promote the migration and invasion of ESCC cells but not proliferation. Furthermore, M2 TAMs were observed to induce EMT in ESCC cells. Together, our results showed that infiltrated M2 TAMs in the stroma is a feature accompanying ESCC metastasis and that M2 TAMs can promote the migration and invasion, but not proliferation, of ESCC cells, thereby inducing EMT. Thus, M2 TAMs could be an alternative therapeutic target in ESCC. Histol Histopathol 34, 563-572 (2019)
Key words: Oesophageal squamous cell carcinoma (ESCC), M2 macrophage, Invasion, Migration, Epithelial-mesenchymal transition (EMT)
DOI: 10.14670/HH-18-061