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CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer

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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.

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Abbreviations

CLM:

Liver metastases of colorectal cancer

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

FC:

Fibrous pseudocapsule

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Acknowledgments

This work was supported in part by grants from the Japan Society for the Promotion of Science (Grant# 19591577, 22591500).

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Authors and Affiliations

  1. Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Nozomu Sakai, Hiroyuki Yoshidome, Takashi Shida, Fumio Kimura, Hiroaki Shimizu, Masayuki Ohtsuka, Dan Takeuchi, Masahiro Sakakibara & Masaru Miyazaki

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  1. Nozomu Sakai
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  2. Hiroyuki Yoshidome
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  3. Takashi Shida
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  4. Fumio Kimura
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  7. Dan Takeuchi
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  8. Masahiro Sakakibara
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  9. Masaru Miyazaki
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Correspondence to Hiroyuki Yoshidome.

Additional information

Nozomu Sakai and Hiroyuki Yoshidome contributed equally to this study.

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Sakai, N., Yoshidome, H., Shida, T. et al. CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer. Clin Exp Metastasis 29, 101–110 (2012). https://doi.org/10.1007/s10585-011-9433-5

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  • DOI: https://doi.org/10.1007/s10585-011-9433-5

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