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

Wiśniewski JR, Ostasiewicz P, Duś K, Zielińska DF, Gnad F, Mann M - Mol. Syst. Biol. (2012)

Bottom Line: 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.Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany. jwisniew@biochem.mpg.de

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.

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Related in: MedlinePlus

Distribution of proteins with significant C/N ratio (P<0.05) representing selected pathways and specific functions. (A) Cellular signaling; (B) DNA replication and repair; (C) regulation of transcription and the spliceosome; (D) translation and the ribosomal proteins; (E) oxidative phosphorylation and glycolysis/gluconeogenesis; (F) plasma membrane channel, extracellular and receptor proteins. Gray background dots show the distribution of all quantified proteins without significant change between cancer and normal tissue.
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f5: Distribution of proteins with significant C/N ratio (P<0.05) representing selected pathways and specific functions. (A) Cellular signaling; (B) DNA replication and repair; (C) regulation of transcription and the spliceosome; (D) translation and the ribosomal proteins; (E) oxidative phosphorylation and glycolysis/gluconeogenesis; (F) plasma membrane channel, extracellular and receptor proteins. Gray background dots show the distribution of all quantified proteins without significant change between cancer and normal tissue.

Mentions: The high number of identified proteins allowed systematic investigation of functional alterations characteristic for colon cancer cells such as signaling pathways, metabolic processes, ion transport, replication, and transcriptional regulation, among many others. Alterations in signaling pathways due to gene mutations are recognized drivers of cancer development, but so far it has been difficult to measure the corresponding proteins directly by quantitative methods. We found that in CRC the WNT, p53, ERBB, or TGFβ pathways are most frequently affected. We identified 147 proteins involved in at least 1 of these pathways; 29 of them were significantly elevated in tumor and none significantly downregulated (Figure 5A). We observed a similar distribution of changes for insulin and chemokine pathways, with a majority of upregulated and only a few downregulated members (Figure 5A). The coverage of key members of these pathways and their quantitative changes is shown in Supplementary Figure 2.


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

Wiśniewski JR, Ostasiewicz P, Duś K, Zielińska DF, Gnad F, Mann M - Mol. Syst. Biol. (2012)

Distribution of proteins with significant C/N ratio (P<0.05) representing selected pathways and specific functions. (A) Cellular signaling; (B) DNA replication and repair; (C) regulation of transcription and the spliceosome; (D) translation and the ribosomal proteins; (E) oxidative phosphorylation and glycolysis/gluconeogenesis; (F) plasma membrane channel, extracellular and receptor proteins. Gray background dots show the distribution of all quantified proteins without significant change between cancer and normal tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472694&req=5

f5: Distribution of proteins with significant C/N ratio (P<0.05) representing selected pathways and specific functions. (A) Cellular signaling; (B) DNA replication and repair; (C) regulation of transcription and the spliceosome; (D) translation and the ribosomal proteins; (E) oxidative phosphorylation and glycolysis/gluconeogenesis; (F) plasma membrane channel, extracellular and receptor proteins. Gray background dots show the distribution of all quantified proteins without significant change between cancer and normal tissue.
Mentions: The high number of identified proteins allowed systematic investigation of functional alterations characteristic for colon cancer cells such as signaling pathways, metabolic processes, ion transport, replication, and transcriptional regulation, among many others. Alterations in signaling pathways due to gene mutations are recognized drivers of cancer development, but so far it has been difficult to measure the corresponding proteins directly by quantitative methods. We found that in CRC the WNT, p53, ERBB, or TGFβ pathways are most frequently affected. We identified 147 proteins involved in at least 1 of these pathways; 29 of them were significantly elevated in tumor and none significantly downregulated (Figure 5A). We observed a similar distribution of changes for insulin and chemokine pathways, with a majority of upregulated and only a few downregulated members (Figure 5A). The coverage of key members of these pathways and their quantitative changes is shown in Supplementary Figure 2.

Bottom Line: 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.Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany. jwisniew@biochem.mpg.de

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.

Show MeSH
Related in: MedlinePlus