Breast cancer growth, invasion and metastasis all are promoted by inflammation. Inflammation can be acute, occurring after injury, infection or exposure to an irritant, or systemic, a persistent state that involves chronic activation of the immune system. Systemic inflammation is known to increase the risk of breast cancer recurrence. However, massive one-time short-term increases in inflammation and repeated acute inflammation also can promote breast cancer metastasis in some circumstances. Now a new study has reported that lung inflammation induced by an allergen promotes pulmonary metastasis in a mouse model of breast cancer.

Every type of breast cancer has the potential to metastasize to the lungs, but pulmonary metastasis is more common in HER2 overexpressing (HER2+) and triple negative (ER-/PR-/HER2-) disease than in hormone receptor positive/HER2- disease (ER+/PR+/HER2-). Chronic inflammatory states such as that associated with type 2 diabetes have been shown to increase the risk of pulmonary metastasis. Metastasis to the lungs is also more frequent in those with inflammatory lung diseases such asthma or emphysema. Cigarette smoking also increases the risk. One study reported that the risk of lung metastases developing increased as the number of cigarettes smoked in a lifetime increased.

Latest research finds allergen-driven inflammation increases lung metastasis

The study referenced at the beginning of this news story was designed to investigate how pre-existing allergen-driven pulmonary inflammation affects breast cancer progression. The authors previously developed a mouse model of breast cancer in which pulmonary inflammation is induced by an allergen before the mice are implanted with cancer cells. In the current study, the authors determined how this pre-existing inflammation altered the pulmonary microenvironment in such a way that tumor metastasis was increased.

Pre-existing pulmonary inflammation was found to be associated with: (1) increased growth of the primary tumor and increased metastasis; (2) increased expression of a glycoprotein known as CHI3L1 (chitinase 3-like protein 1, which has a role in suppressing lung injury with a fibroproliferative response but can also induce the expression of proinflammatory and protumorigenic molecules); and (3) increased levels of myeloid populations in the mouse lungs (myeloid cells in the lungs have a role in preventing spontaneous pulmonary inflammation).

Myeloid-derived cells from the lungs of mice with pre-existing allergic pulmonary inflammation were found to produce higher amounts of CHI3L1 than untreated control mice. The authors also showed that CHI3L1 knockout mice (in which CHI3L1 was inactivated) with allergic pulmonary inflammation had reduced levels of myeloid-derived cells, lower levels of proinflammatory mediators, and a significantly reduced tumor volume and metastasis compared with regular mice with allergen exposure. The authors conclude that pre-existing inflammation and CHI3L1 could set the stage for a premetastatic milieu in the lungs and aid in the support of metastases.

Please see our article on inflammation for more information.