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Colorectal cancer (CRC) is one of the most common types of cancer; it is diagnosed in more than one million people each year and causes the death of about half of them. Early detection can help to decrease CRC-related mortality. In fact, the 5-year survival rate exceeds 90% when the disease is localized and is only 10% in case of metastases. Consequently, it is imperative to improve methods for the early detection of the disease. In this context, genomic approaches have resulted in new CRC biomarkers and have helped to shed light on the genetic basis of cancer as a whole. However, the proteome provides a more dynamic and faithful image of the genetic program of a cell. Hence, given the importance of proteins as effectors of cellular behavior, proteomic analysis has the potential to identify biomarkers that can help to classify and predict CRC. Several proteomic technique, such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), quantitative isotopic protein labeling (SILAC, ICAT, and iTRAQ), and two-dimensional gel electrophoresis (2D-PAGE and 2D-DIGE), are being used in cancer research and can improve the diagnosis of patients; they are also helping to optimize personalized therapy. In this chapter, the main proteomic approaches used in biomarker research will be discussed, together with their impact and potential in the clinical setting. The proteomic biomarkers currently used for CRC diagnosis and/or therapy monitoring will be also described.

Each year, nearly one million people develop colorectal cancer, and 50% of them are expected to die because of cancer within 5 years of diagnosis. Over the last two decades, significant advances in screening, surgery, adjuvant chemotherapy, and patient monitoring have improved the 5-year survival rate. Colorectal cancer is a molecularly heterogeneous disease, and the analysis of its molecular signatures and the identification of colorectal cancer biomarkers will lead to better screening approaches and personalized therapeutic plans. A biomarker is a substance that can be measured and used as an indicator of a biological and/or pathological state. In cancer pathology, biomarkers can be used to detect the disease, to predict prognosis or response to therapy, and to evaluate the efficacy of therapy thereby improving the patient’s life expectancy and quality of life. The carcinoembryonic antigen (CEA) is the biomarker most frequently used in colorectal cancer. It is effective in the surveillance of colorectal cancer patients and in monitoring the efficacy of therapy, whereas it is less useful in colorectal screening. Recent studies indicate that also CEA-related proteins (CEACAMs) are promising potential colorectal cancer biomarkers. CEA and CEACAM proteins play important roles in cancer pathology, and the analysis of their functions will be useful for the identification of diagnostic and/or prognostic factors and therapeutic targets in colorectal and other cancers.

Cancer stem cell characterization represents a breakthrough in cancer research. Despite evidence showing the existence and the role of cancer stem cells in osteosarcoma (OS) onset and progression, little is known about their specific surface phenotype. To address this issue, we carried out a cytometric analysis with an antibody-array comprising 245 membrane proteins comparing the stem and differentiated OS cells. As experimental model, we chose the stem-like cell line 3aminobenzamide-OS and its parental, differentiated, cell line MG63. We identified 50 differentially expressed, 23 homogeneously expressed, and 172 not expressed proteins in the two cell line models, thus defining a surface protein signature specific for each of them. Furthermore, we selected ERK1/2 (p44/42 mitogen-activated protein kinases) as a potential pathway correlated with processes that characterize tumorigenic potential and stemness of 3aminobenzamide-OS cells

BACKGROUND: Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell-directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen-related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell-directed treatment of colorectal cancer. METHODS: First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell-enriched colon spheres. Finally, the effects of small-interfering RNA-mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated. RESULTS: CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133-positive cells that were isolated from normal colon, whereas its expression was brightest (CD66cbright) in CD133-positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66cbright population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells. CONCLUSIONS: CD66cbright expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer. Cancer 2013.

Contains fulltext : 93977.pdf (publisher's version ) (Open Access)

Contains fulltext : 93977.pdf (publisher's version ) (Open Access)

Contains fulltext : 93977.pdf (publisher's version ) (Open Access)