Abstract
We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/ group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.
Highlights
It has been becoming increasingly clear that tumor inflammatory microenvironment is the underlying cause of many types of cancer (Mantovani et al, 2008; Freire et al, 2013; Schauer et al, 2013)
We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms
We demonstrated that TAMs promoted Coal tar pitch (CTP) extract (CTPE)-induced tumorigenecity in vitro using co-culture system of human bronchial epithelial cells (BEAS-2B) and macrophage-like THP-1 cells (Feng et al, 2012)
Summary
It has been becoming increasingly clear that tumor inflammatory microenvironment is the underlying cause of many types of cancer (Mantovani et al, 2008; Freire et al, 2013; Schauer et al, 2013). There have been no studies to show the role of TAMs in initiation, progression and metastasis of lung cancer in vivo far. Activator protein 1 (AP-1) transcription factor is composed of Jun (c-Jun, JunB and JunD) and Fos (c-Fos, FosB, Fra and Fra2) subfamilies. We demonstrated that TAMs promoted CTP extract (CTPE)-induced tumorigenecity in vitro using co-culture system of human bronchial epithelial cells (BEAS-2B) and macrophage-like THP-1 cells (Feng et al, 2012). We evaluated the role of macrophages in the promotion of lung cancer progression and metastasis using a nude mice model that is extensively used as an in vivo tumor model, in which CTPE-induced transformed BEAS-2B cells were injected into nude mice in conjunction with macrophage-like THP-1 cells. We investigated the expression levels of c-Jun in xenograft tumor of nude mice, and analyzed the correlation between c-Jun protein expression levels and angiogenesis, metastasis to explore the implicated mechanism
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