Through scRNA-seq analysis of liver tissues from Microsatellite stable metastatic-type metastatic colorectal cancer (MSS-mCRC), normal liver tissues, and PBMCs, Sathe et al. (34) revealed that SPP1+ macrophages in the metastatic tumor microenvironment (TME) secrete SPP1, which binds to integrin receptors (ITGAV/ITGB1) on cancer-associated fibroblasts (CAFs). Here, SPP1 is linked to metastatic colorectal cancer.