title: Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma.
abstract: We report a proteomic analysis of microdissected material from formalin-fixed and paraffin-embedded colorectal cancer, quantifying > 7500 proteins between patient matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels of 1808 proteins changed significantly between normal and cancer tissues, a much larger fraction than that reported in transcript-based studies. Tumor cells exhibit extensive alterations in the cell-surface and nuclear proteomes. Functionally similar changes in the proteome were observed comparing rapidly growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic remodeling between primary cancer and metastases, suggesting that no drastic proteome changes are necessary for the tumor to propagate in a different tissue context. Additionally, we introduce a new way to determine protein copy numbers per cell without protein standards. Copy numbers estimated in enterocytes and cancer cells are in good agreement with CaCo-2 and HeLa cells and with the literature data. Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany. jwisniew@biochem.mpg.de
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wiśniewski
authors.forename: Paweł
authors.initials: P
authors.lastname: Ostasiewicz
authors.forename: Kamila
authors.initials: K
authors.lastname: Duś
authors.forename: Dorota F
authors.initials: DF
authors.lastname: Zielińska
authors.forename: Florian
authors.initials: F
authors.lastname: Gnad
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D018938:Caco-2 Cells; D002454:Cell Differentiation; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D061346:Laser Capture Microdissection; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D016612:Paraffin Embedding; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D016707:Tissue Fixation; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome