Role of chemokines in hepatocellular carcinoma (Review)

Oncol Rep. 2021 Mar;45(3):809-823. doi: 10.3892/or.2020.7906. Epub 2020 Dec 22.

Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges for the treatment of HCC is the prevention or management of recurrence and metastasis of HCC. It has been found that chemokines and their receptors serve a pivotal role in HCC progression. In the present review, the literature on the multifactorial roles of exosomes in HCC from PubMed, Cochrane library and Embase were obtained, with a specific focus on the functions and mechanisms of chemokines in HCC. To date, >50 chemokines have been found, which can be divided into four families: CXC, CX3C, CC and XC, according to the different positions of the conserved N‑terminal cysteine residues. Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery.

Keywords: hepatocellular carcinoma; metastasis; chemokine; exosomes; targeted treatment.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Chemokines / metabolism*
  • Chemokines / therapeutic use
  • Disease Progression
  • Exosomes / metabolism
  • Exosomes / transplantation
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Molecular Targeted Therapy
  • Receptors, Chemokine / metabolism
  • Receptors, Chemokine / therapeutic use
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Chemokines
  • Receptors, Chemokine

Grants and funding

The present review was supported by the Hebei Provincial Government Clinical Medicine Talents Training and Basic Research Project (grant no. 361003).