Allergic inflammation may promote breast cancer metastasis

It's well known that inflammation contributes to 'flipping the molecular switches' that turn on breast cancer and other malignancies. A study entitled Allergen induced pulmonary inflammation enhances mammary tumor growth and metastasis: Role of CHI3L1 recently published in the Journal of Leukocyte Biology reveals a mechanism by which allergic inflammation can promote breast cancer metastasis. The authors state:

"Metastasis is the primary cause of mortality in women with breast cancer. Metastasis to the lungs is greater in patients with pulmonary inflammatory illnesses. It is unknown how pre-existing pulmonary inflammation affects mammary tumor progression. We developed a novel breast cancer model in which pulmonary inflammation is induced in mice prior to tumor cell implantation."

CHI3L1 associated with allergic inflammation promotes breast cancer metastasis

They had earlier shown that a glycoprotein known as CHI3L1 associated with lung inflammation induces the production of proinflammatory and protumorigenic molecules. Here they show how allergic inflammation alters the lung environment to promote breast cancer metastasis.

"In the present study, we determined how pre-existing allergen-induced inflammation changes the pulmonary microenvironment to exacerbate tumor metastasis. We showed that pre-existing pulmonary inflammation in mammary tumor bearers is associated with: 1) an increase in growth of the primary tumor and metastasis; 2) an increase in the expression of a glycoprotein known as CHI3L1; and 3) increase in the levels of myeloid populations in their lungs. We also showed that myeloid derived cells from the lungs of allergic tumor bearers produce higher amounts of CHI3L1 than the saline controls."

They further demonstrated the key role of CHI3L1 by removing the glycoprotein from the picture:

"In this study, we show that CHI3L1 knockout tumor bearers with pre-existing allergic pulmonary inflammation had decreased levels of myeloid-derived cells, decreased levels of proinflammatory mediators, and a significant reduction in tumor volume and metastasis compared with the wild-type controls."

Targeting allergic inflammation in breast cancer

The authors conclude with a comment on the clinical importance of targeting allergen-induced inflammation in breast cancer management:

"Pre-existing inflammation and CHI3L1 might be driving the establishment of a premetastatic milieu in the lungs and aiding in the support of metastatic foci. Understanding the role of allergen-induced CHI3L1 and inflammation in tumor bearers and its effects on the pulmonary microenvironment could result in targeted therapies for breast cancer."