Metastatic disease is a major cause of death in cancer, and the lung is a common metastatic site. Metastasis can become apparent only years after primary tumor seeding. The lung metastatic niche creates the favourable environment for disseminated tumor cells to invade and acquire dormancy, and comprises alterations in lung resident cells, initiated and maintained by tumor cells and/or immune cells. Recently, increased serum YKL40 was found to be correlated with increased metastasis in numerous cancers. YKL40 is produced by airway epithelial cells, fibroblasts, and myeloid cells and was shown to promote alternative activation of macrophages, key cells in site-specific immunity to metastasis. Therefore, this chitinase-like protein (CLP) could be more than just a biomarker and may promote metastasis that can be targeted. Since mice have multiple functional homologues for YKL40, namely BRP-39 (Chil1, orthologue of YKL40), YM1 (Chil3) and YM2 (Chil4), the role of CLPs in biology and cancer is still unclear. CLPs bind to chitin, heparin, hyaluronan, and collagen and their biological functions include regulation of cell survival, proliferation, adhesion, migration, activation and ECM assembly. Moreover, they play important roles in inflammation, wound healing, and tissue remodelling and are upregulated in various diseases like asthma, infection, and cancer. In this project I aim to clarify the role of the various CLPs in a murine model of metastatic disease, making use of highly unique targeting tools that were developed in-house. Understanding how CLPs and alveolar macrophages create an environment that allows engraftment, dormancy and growth of disseminated tumor cells will provide new therapeutic targets for metastasis prevention.