TIMP1-Mediated M2 Macrophage Polarization Facilitates Liver Metastasis in Colorectal Cancer

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality globally, with liver metastasis (CRLM) accounting for the majority of CRC-associated deaths. Although advances in early detection and treatment have improved outcomes, the prognosis for patients with advanced disease remains dismal. Recent studies have underscored the critical role of the hepatic pre-metastatic niche (PMN) in facilitating CRC dissemination, where M2-polarized macrophages play a central role in promoting immune suppression and metastatic colonization. However, the molecular mechanisms driving M2 polarization in this context remain incompletely understood. Overall design: To explore the immunomodulatory effects of TIMP1 on liver macrophages, we isolated hepatic macrophages from BALB/c mice, treated them with recombinant TIMP1 (rTIMP1) protein for 48 hours, and conducted transcriptomic profiling via RNA sequencing.