Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases

Int J Oncol. 2009 Apr;34(4):923-30. doi: 10.3892/ijo_00000218.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) has been demonstrated to play a role in tumor progression. The present study examined the MCP-1 expression of colorectal liver metastases and determined whether MCP-1 is related to tumor progression and is a predictive marker for survival after hepatic resection of colorectal liver metastases. Eighty-seven patients with colorectal liver metastases were evaluated by immunohistochemistry of MCP-1, Angiopoietin-2, CD68, and CD34 for determination of microvessel density. Clinicopatholgical data were also examined. In a separate experiment, immunohistochemistry of MCP-1 was performed to investigate the expression of primary colorectal tumor according to the clinical stage. MCP-1 mRNA expression was determined in colorectal cancer cell lines. Forty-nine patients (56%) showed high expression of MCP-1 of colorectal liver metastases. High MCP-1 expression was related to multiple colorectal liver metastases. When the degree of MCP-1 expression increased, microvessel density count significantly increased compared with low MCP-1 expression. The MCP-1 expression correlated with Angiopoietin-2 expression. MCP-1 expression of the primary colorectal cancer increased as the clinical stage advanced. The increased MCP-1 mRNA expression was observed in cancer cell lines which have high metastasis potency. Univariate analysis demonstrated that the timing of metastases, tumor size, number of metastases, and MCP-1 expression were significant prognostic factors. Multivariate analysis demonstrated that MCP-1 expression was a significant prognostic factor in hepatic disease-free survival. The MCP-1 expression in colorectal liver metastases, at least in part, may be associated with angiogenesis and be a predictive marker for hepatic recurrence after hepatic resection for colorectal liver metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiopoietin-2 / biosynthesis
  • Antigens, CD / biosynthesis
  • Antigens, CD34 / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / physiology*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neovascularization, Pathologic*
  • Treatment Outcome

Substances

  • Angiopoietin-2
  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Chemokine CCL2