Secreted Clusterin in Colon Tumor Cell Models and Its Potentialas Diagnostic Marker for Colorectal Cancer

We studied the specific changes of the secreted protein clusterin and its cytoplasmic precursor regarding colorectal tumorigenesis, using in vitro differentiation of Caco-2 cells. In tumor-like stage, we observed an overexpression of both precursor and secreted clusterin, corroborated in the cell line SW-480. Noticeably, SW-620 cells (from a tumoral node, thus with metastatic capacity) did not show overexpression of either precursor or secreted clusterin, suggesting a downregulation related to local metastasis. We further investigated clusterin in serum, finding a significant increase in colorectal cancer patients, with 81% sensitivity, 79% specificity, and an area under the ROC curve of 0.85.

[1]  Francesco Rulli,et al.  Clusterin in Stool: A New Biomarker for Colon Cancer Screening? , 2009, The American Journal of Gastroenterology.

[2]  Eugene A. Kapp,et al.  Secretome-based proteomic profiling of Ras-transformed MDCK cells reveals extracellular modulators of epithelial-mesenchymal transition. , 2009, Journal of proteome research.

[3]  J. O’Sullivan,et al.  High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers , 2009, Cancer Epidemiology Biomarkers & Prevention.

[4]  P. Kujala,et al.  Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells , 2008, Histochemistry and Cell Biology.

[5]  M. P. Cadena,et al.  Relevance of Protein Isoforms in Proteomic Studies , 2007 .

[6]  T. Ørntoft,et al.  Clusterin Expression in Normal Mucosa and Colorectal Cancer*S , 2007, Molecular & Cellular Proteomics.

[7]  Wenwen Wu,et al.  Protein Pattern Difference in the Colon Cancer Cell Lines Examined by Two-Dimensional Differential In-Gel Electrophoresis and Mass Spectrometry , 2006, Surgery Today.

[8]  F. J. Rodríguez-Berrocal,et al.  Differential Expression of Serum Clusterin Isoforms in Colorectal Cancer* , 2006, Molecular & Cellular Proteomics.

[9]  R. Taichman,et al.  Clusterin inhibits apoptosis by interacting with activated Bax , 2005, Nature Cell Biology.

[10]  T. Yeatman,et al.  Clusterin-Mediated Apoptosis Is Regulated by Adenomatous Polyposis Coli and Is p21 Dependent but p53 Independent , 2004, Cancer Research.

[11]  M. Páez de la Cadena,et al.  Concanavalin A chromatography coupled to two-dimensional gel electrophoresis improves protein expression studies of the serum proteome. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[12]  F. Pichiorri,et al.  Modulation of different clusterin isoforms in human colon tumorigenesis , 2004, Oncogene.

[13]  R. Stierum,et al.  Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2. , 2003, Biochimica et biophysica acta.

[14]  D. Boothman,et al.  Synthesis and Functional Analyses of Nuclear Clusterin, a Cell Death Protein* , 2003, The Journal of Biological Chemistry.

[15]  I. Trougakos,et al.  Serum levels of the senescence biomarker clusterin/apolipoprotein J increase significantly in diabetes type II and during development of coronary heart disease or at myocardial infarction , 2002, Experimental Gerontology.

[16]  M. Páez de la Cadena,et al.  Activity and properties of alpha-L-fucosidase are dependent on the state of enterocytic differentiation of HT-29 colon cancer cells. , 2002, The international journal of biochemistry & cell biology.

[17]  J. Carver,et al.  Clusterin is an extracellular chaperone that specifically interacts with slowly aggregating proteins on their off‐folding pathway , 2002, FEBS letters.

[18]  C. Stanners,et al.  Control of carcinoembryonic antigen gene family expression in a differentiating colon carcinoma cell line, Caco-2. , 1991, Cancer research.

[19]  S. Mao,et al.  Purification and characterization of apolipoprotein J. , 1990, The Journal of biological chemistry.

[20]  T. Tobe,et al.  Sandwich ELISA assay for quantitative measurement of SP-40,40 in seminal plasma and serum. , 1990, Journal of immunological methods.

[21]  W. Peters,et al.  Time-dependent activity and expression of glutathione S-transferases in the human colon adenocarcinoma cell line Caco-2. , 1989, The Biochemical journal.

[22]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[23]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[24]  A. Gornall,et al.  Determination of serum proteins by means of the biuret reaction. , 1949, The Journal of biological chemistry.

[25]  M. Páez de la Cadena,et al.  Identification of hydrophobic proteins as biomarker candidates for colorectal cancer. , 2007, The international journal of biochemistry & cell biology.

[26]  J. Willis,et al.  Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer , 2006, Cell Death and Differentiation.

[27]  D. Xie,et al.  Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression. , 2005, World journal of gastroenterology.

[28]  M. Scaltriti,et al.  Clusterin (SGP‐2, ApoJ) expression is downregulated in low‐ and high‐grade human prostate cancer , 2004, International journal of cancer.

[29]  M. Pinto,et al.  Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture , 1983 .