Nathalia Gazaniga

Allergen induced pulmonary inflammation enhances mammary tumor growth and metastasis: Role of CHI3L1      

Libreros, S., R. Garcia-Areas, P. Robinson, A. Humbles, and V. Iragavarapu-Charyulu. "876: Allergen Induced Pulmonary Inflammation Enhances Mammary Tumor Growth and Metastasis: Role of CHI3L1." European Journal of Cancer 50 (2014): n. pag. Web.       

 

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 in- flammation is induced in mice prior to tumor cell implan- tation. In the present study, we determined how pre- existing allergen-induced inflammation changes the pul- monary microenvironment to exacerbate tumor metas- tasis. 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 glyco- protein 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. We previously showed that CHI3L1 induces the expression of proinflammatory and protumorigenic mole- cules. 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. Pre-existing inflammation and CHI3L1 might be driving the establishment of a premeta- static 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.

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