Benzopyrene promotes lung cancer A549 cell migration and invasion through up-regulating cytokine IL8 and chemokines CCL2 and CCL3 expression

Abstract

Tobacco-sourced carcinogen including benzopyrene (B[a]P) in lung cancer metastasis has not been fully reported. In this study, lung carcinoma A549 cell line was used to investigate the potential roles of tobacco-sourced B[a]P on cell metastasis and invasion and to assess its underlying mechanism. Effects of tobacco-sourced carcinogen on A549 cell proliferation, metastasis, and invasion were analyzed using MTT assay, Transwell assay, and scratch method, respectively. The effects of tobacco-sourced carcinogen on cytokines and chemokines secretion were detected using enzyme-linked immunosorbent assay. Moreover, correlation between inflammatory factor expression and cancer cell migration and invasion was assessed using siRNA-mediated gene silencing. Data showed that both B[a]P and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone either at high or low dose performed no significant difference on A549 cell proliferation with time increasing. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone performed no significant difference on A549 cell migration and invasion while B[a]P significantly increased A549 cell migration and invasion compared to the control group (P < 0.05). Consequently, except for IL-6, IL-8, CCL-2, and CCL-3, secretions were significantly increased by B[a]P treatment compared to the control (P < 0.05). Furthermore, when CCL-2 and CCL-3 were silenced, the migrated and invasive A549 cells were significantly decreased compared to the control, respectively (P < 0.05), while silenced IL-8 drastically decreased the migrated and invasive cells compared to the control (P < 0.01). Taken together, this study illustrated that there may be significant correlation between smoking and lung cancer metastasis. B[a]P maybe an excellent contributor for lung cancer metastasis through up-regulating IL-8, CCL-2, and CCL-3 expression.

High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma

“…CCL2 could recruit monocytes, memory T cells, and dendritic cells to the sites of inflammation produced either by tissue injury or infection, as well as the tumor microenvironment . CCL2 is produced by a variety of tumors and plays an important role in cancer progression, particularly in promoting cancer cell migration and invasion . Our study showed that CCL2 was highly expressed in the LUAD microenvironment; however, the reason for this is unclear.…”

“…23 CCL2 is produced by a variety of tumors and plays an important role in cancer progression, particularly in promoting cancer cell migration and invasion. 24 Our study showed that CCL2 was highly expressed in the LUAD microenvironment; however, the reason for this is unclear. In Lewis lung carcinoma, TNFα released by tumor cell-activated macrophages is critical for increased CCL2 production by tumor cells.…”

Estrogenic Compounds: Chemical Characteristics, Detection Methods, Biological and Environmental Effects

“…Benzopyrene exposure is associated with pregnancy loss, alterations in fetal development (Zhang et al 2016), alterations in weights of the reproductive organs, damage in ovarian follicles, and infertility and abnormal fetal development in laboratory animal models (Borman et al 2000;Csaba et al 1993; MacKenzie and Angevine 1981; Rigdon and Rennels 1964). Analysis of epigenetic effects of benzopyrene was studied in four breast cancer cell lines (MCF-7, T47-D, MDA MB 231, and HCC-1806) by Sadikovic and Rodenhiser (2006).…”

Filling the gap between chemical carcinogenesis and the hallmarks of cancer: A temporal perspective

“…57 Recently, some studies provided mechanistic clues showing that BaP may contribute to lung cancer cell invasion and metastasis by upregulating proinflammatory chemokines (IL8, CCL-2, CCL-3) and the one of the master regulator of the epithelial-to-mesenchymal transition, Twist. 58,59 Moreover, BaP was able to induce cell migration in triple-negative breast cancer MDA-MB-231 cells through a lipoxygenase-and Src-dependent pathway, notably by increasing the secretion of metalloproteinase MMP-2 and MMP-9. 60 BaP treatment was also able to increase the metastatic potential of hepatocellular carcinoma cell lines in a mouse model, likely through an activation of both angiogenesis and NF-kB pathway.…”