Yi-Fei Wang1,2, Xue-Jian Wang1,3, Zhong Lu1,2, Shu-Rong Liu1,2, Yu Jiang1,2, Xiao-Qing Wan1, Cong-Cong Cheng1,2, Li-Hong Shi1,3, Li-Hua Wang1,2, Yi Ding4,5. 1. Laboratory of Molecular Oncology, Weifang Medical College, Weifang, 261053, Shandong, China. 2. Affiliated Hospital, Weifang Medical University, Weifang, 261053, Shandong, China. 3. Key Laboratory of Applied Pharmacology, Weifang Medical University, Weifang, 261053, Shandong, China. 4. Laboratory of Molecular Oncology, Weifang Medical College, Weifang, 261053, Shandong, China. dingyi6767@163.com. 5. Key Laboratory of Applied Pharmacology, Weifang Medical University, Weifang, 261053, Shandong, China. dingyi6767@163.com.
Abstract
PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.
PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.
Entities:
Keywords:
Breast cancer; Circulating cell-free DNA (cfDNA); Circulating tumor cells (CTCs); EMT; Stat3
Authors: Jie Cheng; Tim Holland-Letz; Markus Wallwiener; Harald Surowy; Katarina Cuk; Sarah Schott; Andreas Trumpp; Klaus Pantel; Christof Sohn; Andreas Schneeweiss; Barbara Burwinkel Journal: Breast Cancer Res Treat Date: 2018-01-16 Impact factor: 4.872
Authors: Dharanija Madhavan; Markus Wallwiener; Karin Bents; Manuela Zucknick; Juliane Nees; Sarah Schott; Katarina Cuk; Sabine Riethdorf; Andreas Trumpp; Klaus Pantel; Christof Sohn; Andreas Schneeweiss; Harald Surowy; Barbara Burwinkel Journal: Breast Cancer Res Treat Date: 2014-05-17 Impact factor: 4.872