Chitinase-3 like-protein-1 CHI3L1 expression associated with pulmonary inflammation accelerates breast cancer metastasis

Disseminated metastasis accounts for a majority of breast cancer deaths. Recently,
elevated serum levels of a glycoprotein known as chitinase-3 like-protein-1 CHI3L1 has been
correlated with poor prognosis in both breast cancer and asthmatic patients. We have combined
mouse models of breast cancer and pulmonary inflammation to determine if CHI3L1 associated
pulmonary inflammation accelerates metastasis. We found that allergic pulmonary inflammation
significantly enhances primary tumor growth in 4T1, 4T07 and 67NR mammary tumors by 10-
fold, while decreasing survival. 4T1 tumor bearers with allergic pulmonary inflammation
showed a 100-fold increase in metastatic tumor formation. We also assessed CHI3L1 levels and
myeloid cells in the lungs of wild type and CHI3L1 knockout mice with allergic pulmonary
inflammation and 4T1 mammary tumors. CHI3L1 levels were higher in the lungs of mammary
tumor bearers with allergic pulmonary inflammation and correlated with increased metastasis.
Wild type mammary tumor bearers with allergic inflammation had higher numbers of myeloid
cells in the lungs in comparison to CHI3L1 knockout tumor bearers with allergic pulmonary
inflammation. CHI3L1 knockout mice tumor bearers had significantly fewer myeloid cells in the
lungs, decreased tumor growth and metastasis, along with increased survival. We propose that
increased CHI3L1 in the lungs attracts myeloid cells that promote tumor growth and breast
cancer metastasis.