The peptide mimicking small extracellular ring domain of CD82 inhibits tumor cell migration in vitro and metastasis in vivo

J Cancer Res Clin Oncol. 2021 Jul;147(7):1927-1934. doi: 10.1007/s00432-021-03595-6. Epub 2021 Apr 2.

Abstract

Background: Tetraspanin KAI1/CD82, a tumor metastasis suppressor, has emerged as a promising molecular target for the management of metastatic disease. However, the peptide mimicking small extracellular ring domain (EC1) of CD82 has not been fully investigated for the function of inhibiting cell migration in vitro and tumor metastasis in vivo.

Methods: Different cancer cells were treated with EC1 mimic peptide in order to detect migration and invasion by the healing assay and transwell. Cell aggregation and adhesion assays were used to investigate the function of homotypic cell-cell aggregation and adhesion to tissue culture plates. Then, we established syngeneic and xenograft animal models to assess the metastasis inhibitory effect of EC1 mimic peptide in vivo.

Results: In vitro studies, the EC1 mimic peptide had been showed to promote homotypic cell-cell aggregation, suppress cell migration, invasion and adherence in multiple tumor cell types. In vivo metastasis assays, the EC1 mimic peptide could strongly inhibit the pulmonary metastasis of LCC in syngeneic mice model and SW620 and H1299 in xenograft mice model.

Conclusion: This novel finding will improve our understanding of the mechanism by which CD82 inhibits metastasis, and suggests that EC1 mimic peptide may be a promising candidate for developing anti-metastasis drugs.

Keywords: CD82; Cancer metastasis; Cell migration; Homotypic cell–cell aggregation; Tumor metastasis suppressor.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement*
  • Cell Proliferation
  • Humans
  • In Vitro Techniques
  • Kangai-1 Protein / metabolism*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Nude
  • Neoplasm Metastasis
  • Peptide Fragments / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • CD82 protein, human
  • Kangai-1 Protein
  • Peptide Fragments