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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

Abundance of proteins matching selected subcellular locations and functions in CaCo-2 cells. The numbers of proteins belonging to each class are given in the parentheses. The protein abundances were calculated on the basis of total spectral intensities of all quantified proteins. Each point represents data from four independent experiments for the 0, 11, and 18 days post confluence. The values for 4 days are for three experiments. Open circles are for linker histone H1 abundance.
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f6: Abundance of proteins matching selected subcellular locations and functions in CaCo-2 cells. The numbers of proteins belonging to each class are given in the parentheses. The protein abundances were calculated on the basis of total spectral intensities of all quantified proteins. Each point represents data from four independent experiments for the 0, 11, and 18 days post confluence. The values for 4 days are for three experiments. Open circles are for linker histone H1 abundance.

Mentions: Sucrase-isomaltase is the standard marker of differentiation in CaCo-2 cells and its transcript levels increase 70 times during this process (Buhrke et al, 2011). Our data revealed a 63- to 68-fold increase of the abundance of this protein between day 0 and days 11 and 18 (Figure 6A), indicating that the cells were well differentiated.


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)

Abundance of proteins matching selected subcellular locations and functions in CaCo-2 cells. The numbers of proteins belonging to each class are given in the parentheses. The protein abundances were calculated on the basis of total spectral intensities of all quantified proteins. Each point represents data from four independent experiments for the 0, 11, and 18 days post confluence. The values for 4 days are for three experiments. Open circles are for linker histone H1 abundance.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Abundance of proteins matching selected subcellular locations and functions in CaCo-2 cells. The numbers of proteins belonging to each class are given in the parentheses. The protein abundances were calculated on the basis of total spectral intensities of all quantified proteins. Each point represents data from four independent experiments for the 0, 11, and 18 days post confluence. The values for 4 days are for three experiments. Open circles are for linker histone H1 abundance.
Mentions: Sucrase-isomaltase is the standard marker of differentiation in CaCo-2 cells and its transcript levels increase 70 times during this process (Buhrke et al, 2011). Our data revealed a 63- to 68-fold increase of the abundance of this protein between day 0 and days 11 and 18 (Figure 6A), indicating that the cells were well differentiated.

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