Secretome compartment is a valuable source of biomarkers for cancer-relevant pathways

Dario Caccia, Laura Zanetti Domingues, Francesca Miccichè, Maida De Bortoli, Cristiana Carniti, Piera Mondellini, Italia Bongarzone

Research output: Contribution to journalArticle

Abstract

In principle, targeted therapies have optimal activity against a specific subset of tumors that depend upon the targeted molecule or pathway for growth, survival, or metastasis. Consequently, it is important in drug development and clinical practice to have predictive biomarkers that can reliably identify patients who will benefit from a given therapy. We analyzed tumor cell-line secretomes (conditioned cell media) to look for predictive biomarkers; secretomes represent a potential source for potential biomarkers that are expressed in intracellular signaling and therefore may reflect changes induced by targeted therapy. Using Gene Ontology, we classified by function the secretome proteins of 12 tumor cell lines of different histotypes. Representations and hierarchical relationships among the functional groups differed among the cell lines. Using bioinformatics tools, we identified proteins involved in intracellular signaling pathways. For example, we found that secretome proteins related to TGF-beta signaling in thyroid cancer cells, such as vasorin, CD109, and βIG-H3 (TGFBI), were sensitive to RPI-1 and dasatinib treatments, which have been previously demonstrated to be effective in blocking cell proliferation. The secretome may be a valuable source of potential biomarkers for detecting cancer and measuring the effectiveness of cancer therapies.

Original languageEnglish
Pages (from-to)4196-4207
Number of pages12
JournalJournal of Proteome Research
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2 2011

Keywords

  • adhesion pathway
  • bioinformatics
  • network prediction
  • predictive biomarkers
  • proteomics
  • secretome
  • signaling pathways
  • targeted therapy

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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