Yan Mei1, Mingdian Wang1, Guanming Lu2, Jiangchao Li3, Lixia Peng1, Yanhong Lang1, Mingming Yang1, Lingbi Jiang3, Changzhi Li1, Lisheng Zheng1, Zhijie Liu1, Dehuan Xie1, Lingling Guo1, Bijun Huang1, Musheng Zeng1, Yanxia Shi4, Chaonan Qian5,6. 1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China. 2. Department of Breast and Thyroid Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Basie, 533000, China. 3. Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, China. 4. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. 5. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China. qianchn@sysucc.org.cn. 6. Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. qianchn@sysucc.org.cn.
Abstract
BACKGROUND: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms. METHODS: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms. RESULTS: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro. CONCLUSION: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.
BACKGROUND: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms. METHODS: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms. RESULTS: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro. CONCLUSION: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.
Authors: Emilie T E Gross; Semi Han; Prasantha Vemu; Carlos D Peinado; Martin Marsala; Lesley G Ellies; Jack D Bui Journal: Oncoimmunology Date: 2016-12-14 Impact factor: 8.110
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396