Abstract 1248: Environmental factors (heavy metal, alcohol) enhance tumor malignant behaviors
Authors: Wang Siying 
Published: August 2015

Abstract
Global cancer incidence and mortality increases dramatically word wild, epically in China, even though significant progress has been made against cancer. Cancer will account for the first most common cause of disease-related death in China. Abundant evidences demonstrated both genetic and environmental factors might contribute to human cancer initiation and progression. In our lab, we focus on role of gain-of-function mutant SHP-2 (genetic factor) and heavy mental contamination or alcohol drinking (environmental factors) on tumor progression. Here, we reported environmental factors like heavy mental arsenic and alcohol consumption promote digestive tumor and breast cancer malignant behaviors. The first, clinic data showed that an increasing arsenic concentration in III/IV TNM stage gastric cancer patient, then an enhanced cancer cell malignant behaviors (proliferation/ motility/ metastasis, etc) were found in gastric cancer or colon cancer cell lines chronic treated with 5-15 nm arsenic in vitro and in vivo. EMT might contribute to this promotion process induced by arsenic.
The second: a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis in Hepatocellular carcinoma (HCC) were found. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC, breast cancer and lewis lung carcinoma (LLC). Specifically, we found that alcohol enhanced the migration/invasion of tumor cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1, activated NF-κB and more infiltrated M2 macrophage was observed in tumor tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. These results suggested that chronic moderate alcohol consumption may promote the progression and metastasis of tumor; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation. Even more, an increasing cancer stem cell population was found in tumor cell lines under low dose alcohol induction.
Our results make us presume chronic stress induced by environmental factors like alcohol, heavy mental, etc might activate cell signal and enhance tumor progression in a universal way. Those studies will be benefited to tumor prevention.
This study was supported by a grant from the National Natural Science Foundation of China (codes: 30873046, 30973424, and 81072663).
Note: This abstract was not presented at the meeting.
Citation Format: Siying Wang. Environmental factors (heavy metal, alcohol) enhance tumor malignant behaviors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1248. doi:10.1158/1538-7445.AM2015-1248