Role of integrin-linked kinase in osteosarcoma progression

J Orthop Res. 2013 Oct;31(10):1668-75. doi: 10.1002/jor.22409. Epub 2013 Jun 19.

Abstract

Although integrin-linked kinase (ILK) has been suggested to play a role in the tumorigenesis of a number of human epithelial carcinomas, little is known of its role in musculoskeletal sarcoma. The authors studied ILK expression by immunohistochemistry using osteosarcoma prechemotherapy specimens from 56 patients, and investigated the prognostic implications of the findings obtained. It was found that ILK overexpression was significantly correlated with the presence of distant metastasis (p = 0.008) and that it was an independent prognostic factor for both poor overall survival and poor event-free survival (p = 0.015 and 0.010, respectively). During a transfection experiment conducted by transfecting osteosarcoma cells with ILK siRNA, VEGF concentrations were measured using an ELISA kit, and then compared with those of untransfected controls to evaluate its angiogenic effects. In addition, apoptotic percentages were measured by Annexin-V flow cytometry, and invasive properties were evaluated by measuring the numbers of non-migrating cells in a Boyden chamber. It was found that ILK downregulation significantly decreased angiogenesis, increased apoptosis, and decreased invasiveness of osteosarcoma cells. These results show that ILK is a promising prognostic factor in osteosarcoma and a novel potential therapeutic target for the treatment of osteosarcoma.

Keywords: angiogenesis; apoptosis; integrin-linked kinase; invasion; osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Osteosarcoma / secondary
  • Prognosis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / genetics
  • Young Adult

Substances

  • RNA, Small Interfering
  • integrin-linked kinase
  • Protein-Serine-Threonine Kinases