Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity

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.

Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung

“…To model metastasis of mammary cancer we used the MMTV- PyMT mouse model, in which polyomavirus middle T antigen is expressed specifically in the mammary epithelium resulting in formation of mammary adenocarcinomas that recapitulate the progression of human breast cancer subtypes with poor prognoses [22–24]. Importantly, when expressed in an FVB/N mouse strain, this results in mammary tumours with high propensity to metastasise to the lungs [25]. Comparing serum from MMTV- PyMT female mice bearing mammary tumours to age-matched non-tumour bearing FVB/N controls, 214 compounds were identified as being significantly altered in mammary tumour bearing animals (Figure S1).…”

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling

“…It is noteworthy that the body weight of the mice remained which was not affected by UTI (Figure 3e). Another orthotopic mammary tumor metastasis model of MMTV‐PyMT mice was used to validate the antimetastasis effect of UTI (Mei et al, 2021). In this model, the lung metastatic foci were significantly reduced by UTI treatment in this model (Figure 4e,f) whereas, the body weight alteration was insignificant compared with the placebo treatment group (Figure 4g).…”

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

“…Interleukin-6 (IL6) has also been implicated in mammary tumors from mice fed a HFD [ 38 ] and in tumor cell lines derived from MMTV-K-Ras mice [ 39 ]. Due to the significance of the local immune environment in breast cancer progression [ 40 ], with findings that also show its role in the MMTV-PyMT model [ 41 ], additional studies on the tumor microenvironment and inflammatory cytokines could help to elucidate mechanisms contributing to the observed differences in metastases.…”