Carbonic anhydrase 13 suppresses bone metastasis in breast cancer

Cancer Treat Res Commun. 2021:27:100332. doi: 10.1016/j.ctarc.2021.100332. Epub 2021 Feb 9.

Abstract

Metastatic progression is the leading cause of mortality in breast cancer. However, molecular mechanisms that govern this process remain unclear. In this study, we found that carbonic anhydrase 13 (CA13) plays a potential role in suppressing bone metastasis. iRFP713-labeled iCSCL-10A (iRFP-iCSCL-10A) breast cancer cells, which exhibit the hallmarks of cancer stem cells, exerted the ability of bone metastasis in hind legs after 5-week injections, whereas no metastasis was observed in control iRFP713-labeled MCF-10A (iRFP-MCF10A) cells. Transcriptome analysis indicated that the expression of several genes, including metabolism-related CA13, was reduced in bone metastatic iRFP-iCSCL-10A cells. In vitro and in vivo analyses demonstrated that overexpression of CA13 in iRFP-iCSCL-10A cells suppressed migration, invasion, and bone metastasis, together with the reduction of VEGF-A and M-CSF expression. Furthermore, we found that breast cancer patients with a low CA13 expression had significantly shorter overall survival and disease-free survival rates compared to those with higher CA13 expression. These findings suggest that CA13 may act as a novel prognostic biomarker and would be a therapeutic candidate for the prevention of bone metastasis in breast cancer.

Keywords: Bone metastasis; Breast cancer; CA13; Invasion; Migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Carbonic Anhydrases / analysis
  • Carbonic Anhydrases / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophage Colony-Stimulating Factor / genetics
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Survival Rate
  • Vascular Endothelial Growth Factor A / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • CSF1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Macrophage Colony-Stimulating Factor
  • CA13 protein, human
  • Carbonic Anhydrases