Multitype network-guided target controllability in phenotypically characterized osteosarcoma: Role of tumor microenvironment

Ankush Sharma, Caterina Cinti, Enrico Capobianco

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

This study highlights the relevance of network-guided controllability analysis as a precision oncology tool. Target controllability through networks is potentially relevant to cancer research for the identification of therapeutic targets. With reference to a recent study on multiple phenotypes from 22 osteosarcoma (OS) cell lines characterized both in vitro and in vivo, we found that a variety of critical proteins in OS regulation circuits were in part phenotype specific and in part shared. To generalize our inference approach and match cancer phenotypic heterogeneity, we employed multitype networks and identified targets in correspondence with protein sub-complexes. Therefore, we established the relevance for diagnostic and therapeutic purposes of inspecting interactive targets, namely those enriched by significant connectivity patterns in protein sub-complexes. Emerging targets appeared with reference to the OS microenvironment, and relatively to small leucine-rich proteoglycan members and D-type cyclins, among other collagen, laminin, and keratin proteins. These described were evidences shared across all phenotypes; instead, specific evidences were provided by critical proteins including IGFBP7 and PDGFRA in the invasive phenotype, and FGFR3 and THBS1 in the colony forming phenotype.

Original languageEnglish (US)
Article number918
JournalFrontiers in immunology
Volume8
Issue numberJUL
DOIs
StatePublished - Jul 31 2017

Keywords

  • Multitype networks
  • Osteosarcoma cell lines
  • Protein network tomography
  • Target controllability
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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