Postponing Tumor Onset and Tumor Progression Can Be Achieved by Alteration of Local Tumor Immunity

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2021 Feb 11

PMID 33568170

Citations 1

Authors

Yan Mei

Mingdian Wang

Guanming Lu

Jiangchao Li

Lixia Peng

Yanhong Lang

Mingming Yang

Lingbi Jiang

Changzhi Li

Lisheng Zheng

Zhijie Liu

Dehuan Xie

Lingling Guo

Bijun Huang

Musheng Zeng

Yanxia Shi

Chaonan Qian

Affiliations

Soon will be listed here.

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.

Citing Articles

A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.

Velazquez F, Viscardi V, Montemage J, Zhang L, Trocchia C, Delamont M Nutrients. 2021; 13(7).

PMID: 34371939 PMC: 8308868. DOI: 10.3390/nu13072431.

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