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Purpose: We previously reported that loss of SMAD4 promotes chemokine CCL15 expression to recruit CCR1⁺ myeloid cells via the CCL15–CCR1 axis, which facilitates metastasis of colorectal cancer to the liver. The purposes of this study were to investigate whether essentially the same mechanism works in tumor invasion of the primary colorectal cancer and to evaluate the clinical importance of CCL15 expression and CCR1⁺ cell accumulation.

Experimental Design: Using human colorectal cancer cell lines with reduced expression of SMAD4 or CCL15, we investigated tumor growth activities in vivo. We used immunohistochemistry (IHC) to investigate expression of SMAD4, CCL15, and CCR1 with 333 clinical specimens of primary colorectal cancer. We next characterized the CCR1⁺ cells using double immunofluorescence staining with several specific cell-type markers. Finally, we …