Permanent coronary artery ligation induced HFrEF in 5 of 9 surviving mice but did not significantly alter mammary tumor growth rates compared to sham surgery in an immunodeficient model.
Does myocardial infarction-induced heart dysfunction affect tumor growth in an immunodeficient mouse model?
In an immunodeficient mouse model, MI-induced HFrEF did not have a clear immune-independent effect on mammary tumor growth, though some modulation of cancer cell proliferation and apoptosis was observed.
Abstract Background Heart failure (HF) and cancer are closely linked, sharing risks and biological pathways. Evidence shows that HF can actively promote tumor growth. However, it is unclear whether experimental HF acts by modulating anti-tumor immune responses or directly affects tumorigenesis. Purpose Using immunodeficient nude mice, this study explores how myocardial infarction–induced heart dysfunction influences the development of human breast cancer xenografts. Methods Female BALB/c athymic nude mice were used to generate a xenograft mouse cancer model in presence (CAL group, n=14) or absence (SHAM group, n=8) of permanent ligation of coronary artery (CAL). A xenograft of mammary adenocarcinoma cell line MCF7 was injected in both groups and tumor growth was weekly recorded for 6 weeks. Estradiol supplementation was permanent after the implantation of estrogen pellet (Figure 1A). Cardiac function was assessed by transthoracic echocardiography. At sacrifice, hearts and tumor mass were collected for ex vivo analysis: infarct areas and heart weights and the physical, histological and molecular features of tumors. Results At the experimental end point, 9/14 CAL mice were alive and a reduced ejection fraction was established in 5/9 (HFrEF CAL group). Whole body and tumor growth rates resulted similar between HFrEF CAL and SHAM mice (Figure 1B), while the heart-to-body weight ratio was higher in HFrEF CAL group. In immunohistochemical and molecular analyses there was a trend for reduced apoptosis, with a lower amount of activated Caspase-3 and a lower cleaved-to-total Caspase-3 ratios, in tumors from HFrEF CAL animals (Figure 1C). In addition, RNAseq data showed an enrichment of genes related to proliferation in these tumors (Figure 1D). Conclusion We did not find evidence of a clear, immune-independent effect of CAL-induced HFrEF on mammary tumor growth, although some modulation of proliferation and apoptosis of cancer cells may occur (Figure 1E).Figure 1For image description, please refer to the figure legend and surrounding text.
Bianconi et al. (Fri,) conducted a other in Myocardial infarction-induced heart dysfunction and breast cancer (n=22). Permanent ligation of coronary artery (CAL) vs. SHAM surgery was evaluated on Tumor growth rate. Permanent coronary artery ligation induced HFrEF in 5 of 9 surviving mice but did not significantly alter mammary tumor growth rates compared to sham surgery in an immunodeficient model.