Hymenolepis diminuta-based helminth therapy in C3(1)-TAg mice does not alter breast tumor onset or progression

Abstract

Background and objectives: An individual's risk of breast cancer is profoundly affected by evolutionary mismatch. Mismatches in Western society known to increase the risk of breast cancer include a sedentary lifestyle and reproductive factors. Biota alteration, characterized by a loss of biodiversity from the ecosystem of the human body as a result of Western society, is a mismatch known to increase the risk of a variety of inflammation-related diseases, including colitis-associated colon cancer. However, the effect of biota alteration on breast cancer has not been evaluated.

Methodology: In this study, we utilized the C3(1)-TAg mouse model of breast cancer to evaluate the role of biota alteration in the development of breast cancer. This model has been used to recapitulate the role of exercise and pregnancy in reducing the risk of breast cancer. C3(1)-TAg mice were treated with Hymenolepis diminuta, a benign helminth that has been shown to reverse the effects of biota alteration in animal models.

Results: No effect of the helminth H. diminuta was observed. Neither the latency nor tumor growth was affected by the therapy, and no significant effects on tumor transcriptome were observed based on RNAseq analysis.

Conclusions and implications: These findings suggest that biota alteration, although known to affect a variety of Western-associated diseases, might not be a significant factor in the high rate of breast cancer observed in Western societies.

Lay summary: An almost complete loss of intestinal worms in high-income countries has led to increases in allergic disorders, autoimmune conditions, and perhaps colon cancer. However, in this study, results using laboratory mice suggest that loss of intestinal worms might not be associated with breast cancer.

Keywords: breast cancer; evolutionary mismatch; helminth therapy; hygiene hypothesis; mouse model.

Figure 1.

The effect of HDC-based helminth therapy on tumor free survival curves in female (A) and male (B) C3(1)-TAg mice No statistically significant difference between the treatment group and the controls was observed: P-values were 0.45 and 0.71 for females and males, respectively [log-rank (Mantel-Cox) test]

Figure 2.

The effect of HDC-based helminth therapy on (A) time to onset of tumor and (B) growth rate of tumors in female C3(1)-TAg mice The time for the tumor to grow in size from the point of detection to 1.00 cm³ was used as a measure of growth rate. No statistically significant difference between the treatment group and the controls was observed: P-values were 0.59 and 0.47 for the time to onset and the growth rate, respectively (t-test)

Figure 3.

Volcano plots comparing gene expression between tumors from female C3(1)-TAg mice treated with and without HDC-based helminth therapy The pairwise comparison was performed using a Student’s t-test. None of the genes showed a significant difference in false discovery rate (FDR) between the two groups.