Abstract 2710: Pulmonary inflammation associated with Chitinase-3-like-1 protein (CHI3L1) expression accelerates breast cancer metastasis to the lung

Metastasis of a primary tumor to distant organs is the principal cause of mortality in patients with breast cancer. Recently, it was reported that asthmatic patients have a greater propensity to develop distant metastasis to the lung. Using a ragweed pulmonary inflammation model, we found that asthmatic mice implanted with 4T1 mammary tumors have a 5-fold increase in formation of metastatic foci in their lungs compared to non-asthmatic 4T1 mammary tumor-bearing mice. Further, asthmatic tumor-bearing mice showed accelerated tumor growth and shorter disease-free survival. We have previously reported that Chitinase-3 like-1 protein (CHI3L1) expression is increased in mammary tumor-bearing mice and that it induces production of prometastatic mediators, CCL2, CXCL2 and MMP-9 by macrophages. Asthmatic patients have been reported to exhibit elevated levels of CHI3L1 in their lungs and circulation while in breast cancer patients these levels are further elevated. We found that the levels of CHI3L1 are higher in circulation and lungs of asthmatic mammary tumor-bearers compared to mice with either asthma or tumor alone. It is unknown if exposure to high levels of CHI3L1 previous to tumorigenesis accelerates metastasis. We hypothesize that CHI3L1-induced pulmonary inflammation generates the proper environment for recruiting circulating breast cancer cells as well as proinflammatory leukocytes (M2 macrophages and myeloid derived suppressors), resulting in increased rate of metastasis to the lung. Treatment of 4T1 asthmatic mammary tumor-bearing mice with chitin microparticles, the ligand of CHI3L1, resulted in decreased levels of metastasis to the lung. These studies provide an understanding of the role of CHI3L1 and existing inflammation in accelerating metastasis, the major cause of death in breast cancer patients. Citation Format: Stephania Libreros, Ramon Garcia-Areas, Roberto Carrio, Vijaya Iragavarapu-Charyulu. Pulmonary inflammation associated with Chitinase-3-like-1 protein (CHI3L1) expression accelerates breast cancer metastasis to the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2710. doi:10.1158/1538-7445.AM2013-2710