Exosomal ANXA1 derived from thyroid cancer cells is associated with malignant transformation of human thyroid follicular epithelial cells by promoting cell proliferation

Int J Oncol. 2021 Dec;59(6):104. doi: 10.3892/ijo.2021.5284. Epub 2021 Nov 15.

Abstract

Exosomes are nano‑sized extracellular vesicles that can be released from cancer cells. It has been shown that cancer cell‑derived exosomes may be associated with carcinogenesis by transferring signaling proteins from malignant to neighboring non‑malignant cells. In addition, annexin A1 (ANXA1) is a well‑known oncogene, that can be released from extracellular vesicles by cancer cells. However, the role of exosomal ANXA1 in the cell‑to‑cell communication of thyroid cancer and thyroid follicular epithelial cells remains unclear. In the present study, the protein expression levels of ANXA1 in thyroid cancer cells and thyroid cancer cell‑derived exosomes were analyzed using western blot analysis. In addition, Cell Counting Kit‑8 and Transwell assays were used to determine cell viability and invasion, respectively. The protein expression levels of ANXA1 were increased in thyroid cancer tissues and thyroid cancer cell lines. In addition, overexpression of ANXA1 significantly increased the proliferation and invasion of the SW579 cells, while knockdown of ANXA1 expression exerted the opposite results. Furthermore, ANXA1 was transferred from the SW579 cells to the Nthy‑ori3‑1 cells via exosomes. Exosomal ANXA1 markedly promoted the proliferation, invasion and epithelial‑to‑mesenchymal transition of the Nthy‑ori3‑1 cells. In addition, SW579 cell‑derived exosomal ANXA1 promoted tumor growth in a xenograft mouse model. Collectively, these findings indicated that SW579 cell‑derived exosomal ANXA1 promoted thyroid cancer development and Nthy‑ori3‑1 cell malignant transformation. Therefore, these findings may aid in the development of effective treatment methods for thyroid cancer.

Keywords: annexin A1; exosome; malignant transformation; thyroid cancer.

MeSH terms

  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / metabolism
  • Adenocarcinoma, Follicular / pathology*
  • Aged
  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Communication
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Epithelial-Mesenchymal Transition
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • ANXA1 protein, human
  • Annexin A1
  • Biomarkers, Tumor

Grants and funding

This work was supported by Scientific and Innovative Action Plan of Shanghai (21ZR1412000).