title: Secretome compartment is a valuable source of biomarkers for cancer-relevant pathways.
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.
authors.affiliation: Proteomics Laboratory, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Caccia
authors.forename: Laura
authors.initials: L
authors.lastname: Zanetti Domingues
authors.forename: Francesca
authors.initials: F
authors.lastname: Miccichè
authors.forename: Maida
authors.initials: M
authors.lastname: De Bortoli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
authors.forename: Piera
authors.initials: P
authors.lastname: Mondellini
authors.forename: Italia
authors.initials: I
authors.lastname: Bongarzone
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology; D000069439:Dasatinib; D030562:Databases, Protein; D006801:Humans; D042541:Intracellular Space; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000032:analysis / Q000737:chemistry; D009369:Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism*; D019000:Phosphotyrosine / Q000032:analysis / Q000737:chemistry; D020543:Proteome / Q000032:analysis* / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; D011743:Pyrimidines; D013844:Thiazoles; D016212:Transforming Growth Factor beta; D019000:Phosphotyrosine; D000069439:Dasatinib