title: CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer.
abstract: Interaction between CXCR4 and CXCL12 plays a role in tumor progression. The present study examined CXCR4, CXCL12 and CD133 expression in liver metastases of colorectal cancer (CLM) and determined whether the expression profiles affect the tumor microenvironment and thus progression, and whether they could serve as a prognostic marker for survival. Liver metastases of colorectal cancer collected from 92 patients were evaluated by CXCR4, CXCL12 and CD133 immunohistochemistry and clinicopathological data were analyzed. The expression profile of CXCR4 was determined in the colorectal cancer cell line, SW48. The expression of cytoplasmic CXCR4 was higher in 36 (39%) patients than that indicated by CXCR4 staining intensity of hepatocytes. High levels of nuclear CXCR4 expression in 23 (25%) patients significantly correlated with CXCL12 expression in hepatocytes. Nuclear CXCR4 expression was increased in the cancer cells after exposure to CXCL12. Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM. The expression of CXCR4 and CXCL12 in CLM may have an interactive effect that could alter the tumor microenvironment. CXCR4 expression in metastatic liver tumors together with the upregulation of CXCL12 in hepatocytes may help to predict the clinical outcomes of patients with CLM after hepatectomy.
authors.affiliation: Department of General Surgery, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Sakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Takashi
authors.initials: T
authors.lastname: Shida
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D054377:Chemokine CXCL12 / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
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