Loss of SMAD4 promotes expression of CCL15 by CRC and recruitment of CCR1+ TANs (CCL15-CCR1 axis) with both arginase-1 (ARG-1) and matrix metalloprotease 9 (MMP-9) activity, forming a premetastatic niche for the disseminated tumor cells [54,55]—e.g., in the lungs [56]. Here, MMP9 is linked to neoplasm.