The relation between ACKR4 and CCR7 genes expression and breast cancer metastasis

Life Sci. 2021 Aug 15:279:119691. doi: 10.1016/j.lfs.2021.119691. Epub 2021 Jun 5.

Abstract

Aims: Breast cancer is the most severe malignant tumor in women. Chemokines and their receptors appear to be implicated in tumorigenesis and metastatic pattern. Also the scavenger atypical chemokine receptors are emerging as crucial regulators for the availability of chemokines. Therefore the aim of the present study is to evaluate the expression of CCR7, ACKR4 and their ligand; CCL21 in human breast cancer.

Main methods: In this study, RT-PCR was done to detect the expression of CCR7 and ACKR4 in 50 non-metastatic and 30 metastatic breast cancer tissue. Also CCL21 level in the serum of study group was detected by ELISA. The expression of all markers is compared to 80 control healthy individual.

Key findings: Our results revealed the increase in expression of CCR7 and CCL21 level in metastatic group compared to non-metastatic and control groups while ACKR4 expression is significantly increased in breast tissues of non-metastatic patients compared to both control and metastatic groups. Also there was significant positive correlation between CCR7 expression and CCL21 level in cancer patients and significant negative correlation between ACKR4 and both CCR-7 and CCL21 in both non-metastatic and metastatic cancer groups.

Significance: Thus, it might be elucidating that ACKR4 and CCR7 could be a novel target for tumor therapy as targeting the chemokine-receptors axis might represent a powerful tool to prevent infiltration and metastasis and consequently improve cancer prognosis and treatment.

Keywords: ACKR4; Atypical chemokine receptors; Breast cancer; CCL21; CCR7; Metastasis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Chemokine CCL21 / genetics
  • Chemokine CCL21 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Receptors, CCR / genetics
  • Receptors, CCR / metabolism*
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Young Adult

Substances

  • ACKR4 protein, human
  • Biomarkers, Tumor
  • CCL21 protein, human
  • CCR7 protein, human
  • Chemokine CCL21
  • Receptors, CCR
  • Receptors, CCR7