The role of fibroblast activation protein in progression and development of osteosarcoma cells

Clin Exp Med. 2020 Feb;20(1):121-130. doi: 10.1007/s10238-019-00591-6. Epub 2019 Nov 19.

Abstract

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

Keywords: AKT signaling pathway; Fibroblast activation protein; Invasion; Migration; Osteosarcoma; Proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Endopeptidases
  • Female
  • Gelatinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Serine Endopeptidases / metabolism*
  • Signal Transduction
  • Up-Regulation*

Substances

  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases