Introduction
Obesity is a risk factor for hormone-sensitive breast cancer, especially in post-menopausal women. The peritumoral obese white adipose tissue attracts a variety of innate and adaptive immune cells. One of the overrepresented cells are mast cells. The role of mast cells and the produced histamine in obese postmenopausal breast cancer has not been investigated.
Methods
To understand the effects of mast cells in obese postmenopausal breast cancer, we ovariectomized 6-weeks-old C57BL/6 wild-type mice and fed them either a regular diet (RD) or a high fat died (HFD) to induce obesity in postmenopausal mice. After the onset of obesity, we injected orthotopically syngeneic Py230 breast cancer cells in the 4th mammary gland. In order to investigate whether the effects of obesity on tumour progression and metastasis were reversible, we performed a weight gain-and-loss experiment. We blocked mast cells degranulation in vivo using sodium cromolyn during tumour progression. We assessed tumour progression and the formation of lung metastases. We analysed the tumour parenchyma by immunohistochemistry and qPCR.
Result
Our results show that obesity promotes mammary tumour growth and lung metastases. In obese mice, we observed an increase in tumour recruitment of mast cells. Weight loss or treatment of obese mice with sodium cromolyn could reverse these effects. In obese mice high quantity of mast cells induces tumour growth and metastasis. In obese, cromolyn treated mice, we observed an increased recruitment of CD8+ T cells. Tumours in obese mice express the histamine receptors H2R and H4R.
Conclusions
Obesity promotes the recruitment of mast cells to the tumour side, which have a negative impact on tumour control in obesity-associated postmenopausal breast cancer. Our results indicate that mast cells act not by activating proliferation or inducing EMT, but rather through the promotion of cancer related immunosuppression. Weight loss or treatment with sodium cromolyn can reverse these effects. These results may have a relevant impact on breast cancer treatment in obese postmenopausal individuals.