Assessment of CMKLR1 level in colorectal cancer and its correlation with angiogenic markers

Exp Mol Pathol. 2020 Apr:113:104377. doi: 10.1016/j.yexmp.2020.104377. Epub 2020 Jan 9.

Abstract

Introduction: Colorectal cancer (CRC) is the second most common malignant neoplasm in men and third in women. It is also the third leading cause of cancer-related death, killing annually >700,000 patients in the world. The global burden of CRC is expected to increase by 60% to >2.2 million new cases and 1.1 million deaths by 2030. The pathogenesis of cancer mainly depends on angiogenesis. This process plays a key role in the growth and infiltration of tumors which is essential for distant metastases. A large number of biochemical pathways is involved in the regulation of angiogenesis. As a subject of our study, we chose chemerin/chemokine-like receptor 1 (CMKLR1) pathway which is responsible for the angiogenic processes in malignant neoplasms.

Aim of the study: To assess the CMKLR1 level and the concentrations of the two markers of angiogenesis, matrix metalloproteinase (MMP)-9 and vascular cell adhesion molecule (VCAM)-1, in tumor and margin tissues of CRC in relation to histological grade and TNM classification.

Materials and methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determine the concentration of CMKLR1, MMP-9, and VCAM-1, we used the commercially available enzyme-linked immunosorbent assay kit.

Results: We found a significantly higher concentration of CMKLR1 and MMP-9 in tumor tissue compared to margin. There was no difference in VCAM-1 concentration between tumor and margin. The margin concentration of CMKLR1 was significantly correlated with that of both MMP-9 and VCAM-1. The margin concentration of VCAM-1 was correlated with that of MMP-9. Additionally, we observed that the tumor levels of CMKLR1 and MMP-9 were positively correlated with the tumor size (T parameter).

Conclusion: CMKLR1 activity may be associated with the angiogenic process in CRC via MMP-9 activity. Further research, involving a larger sample, may verify whether chemerin/CMKLR1 axis could be considered as a suitable target in novel molecular therapies.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Margins of Excision
  • Matrix Metalloproteinase 9 / metabolism
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Receptors, Chemokine / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Biomarkers, Tumor
  • CMKLR1 protein, human
  • Receptors, Chemokine
  • Vascular Cell Adhesion Molecule-1
  • Matrix Metalloproteinase 9