title: Characterization of breast cancer interstitial fluids by TmT labeling, LTQ-Orbitrap Velos mass spectrometry, and pathway analysis.
abstract: Cancer is currently considered as the end point of numerous genomic and epigenomic mutations and as the result of the interaction of transformed cells within the stromal microenvironment. The present work focuses on breast cancer, one of the most common malignancies affecting the female population in industrialized countries. In this study, we perform a proteomic analysis of bioptic samples from human breast cancer, namely, interstitial fluids and primary cells, normal vs disease tissues, using tandem mass tags (TmT) quantitative mass spectrometry combined with the MudPIT technique. To the best of our knowledge, this work, with over 1700 proteins identified, represents the most comprehensive characterization of the breast cancer interstitial fluid proteome to date. Network analysis was used to identify functionally active networks in the breast cancer associated samples. From the list of differentially expressed genes, we have retrieved the associated functional interaction networks. Many different signaling pathways were found activated, strongly linked to invasion, metastasis development, proliferation, and with a significant cross-talking rate. This pilot study presents evidence that the proposed quantitative proteomic approach can be applied to discriminate between normal and tumoral samples and for the discovery of yet unknown carcinogenesis mechanisms and therapeutic strategies.
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Graecia University , viale Europa loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Raso
authors.forename: Carlo
authors.initials: C
authors.lastname: Cosentino
authors.forename: Marco
authors.initials: M
authors.lastname: Gaspari
authors.forename: Natalia
authors.initials: N
authors.lastname: Malara
authors.forename: Xuemei
authors.initials: X
authors.lastname: Han
authors.forename: Daniel
authors.initials: D
authors.lastname: McClatchy
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Maria
authors.initials: M
authors.lastname: Renne
authors.forename: Nuria
authors.initials: N
authors.lastname: Vadalà
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Prati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.forename: Francesco
authors.initials: F
authors.lastname: Amato
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008970:Molecular Weight; D003557:Phyllodes Tumor / Q000378:metabolism*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D013194:Staining and Labeling; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome