Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma

TY - JOUR

T1 - Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma

AU - Wiśniewski, J.R.

AU - Ostasiewicz, P.

AU - Duś, K.

AU - Zielińska, D.F.

AU - Gnad, F.

AU - Mann, M.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84872685287&partnerID=8YFLogxK

U2 - 10.1038/msb.2012.44

DO - 10.1038/msb.2012.44

M3 - Journal article

C2 - 22968445

AN - SCOPUS:84872685287

SN - 1744-4292

VL - 8

JO - Molecular Systems Biology

JF - Molecular Systems Biology

M1 - 611

ER -