Expression of Duffy antigen receptor for chemokines (DARC) is down-regulated in colorectal cancer

J Recept Signal Transduct Res. 2015;35(5):462-7. doi: 10.3109/10799893.2015.1009113. Epub 2015 Jun 22.

Abstract

Duffy antigen receptor for chemokines (DARC) is a silent chemokine receptor which selectively binds angiogenic chemokines without inducing conventional signaling responses. DARC has been reported to inhibit the development of multiple cancers through clearance of angiogenic chemokines. However, its role in colorectal cancer (CRC) remains unclear. We investigated the expression of DARC in CRC and explored correlation of DARC expression with clinical pathological features and microvessel density (MVD). The protein expression levels of DARC were detected by immunohistochemistry in 90 CRC and 64 paired unaffected tissues. The mRNA levels of DARC were detected by quantitative real-time PCR in 15 CRC and paired unaffected tissues. MVD in CRC was also assessed by immunohistochemistry of CD34. We found that the mRNA and protein expression levels of DARC were significantly lower in CRC than in the unaffected tissues (p < 0.05). The DARC protein expression levels were positively correlated with DARC mRNA expression levels in both CRC (p < 0.001) and unaffected tissues (p < 0.001). We also found that DARC expression was significantly correlated with tumor differentiation (p < 0.001), lymph node metastasis (p < 0.01) and TNM stage (p < 0.05). Moreover, we observed a strong negative relationship between DARC expression and MVD in CRC (p < 0.001). We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC.

Keywords: Angiogenesis; DARC; colorectal cancer; microvessel density.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Down-Regulation
  • Duffy Blood-Group System / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Receptors, Cell Surface / metabolism*

Substances

  • ACKR1 protein, human
  • Antigens, CD34
  • Duffy Blood-Group System
  • Receptors, Cell Surface