Toponome mapping in prostate cancer: detection of 2000 cell surface protein clusters in a single tissue section and cell type specific annotation by using a three symbol code.

The toponome imaging technology MELC/TIS was applied to analyze prostate cancer tissue. By cyclical imaging procedures, we detected 2100 cell surface protein clusters in a single tissue section. This study provides the whole data set, a new kind of high dimensional data space, solely based on the structure-bound architecture of an in situ protein network, a putative fraction of the tissue code of prostate cancer. It is visualized as a colored mosaic composed of distinct protein clusters, together forming a motif expressed exclusively on the cell surface of neoplastic cells in prostate acini. Cell type specific expression of this motif, found in this preliminary study, suggests that high-throughput toponome analyses of a larger number of cases will provide insight into disease specific protein networks.

[1]  Walter Schubert,et al.  A three‐symbol code for organized proteomes based on cyclical imaging of protein locations , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[2]  W. Schubert Exploring molecular networks directly in the cell , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[3]  Z. Darżynkiewicz,et al.  Caffeine dissociates complexes between DNA and intercalating dyes: application for bleaching fluorochrome-stained cells for their subsequent restaining and analysis by laser scanning cytometry. , 2001, Cytometry.

[4]  L. Zou,et al.  Immunoglobulin Fcγ receptor promotes immunoglobulin uptake, immunoglobulin‐mediated calcium increase, and neurotransmitter release in motor neurons , 2002, Journal of neuroscience research.

[5]  J. Epstein,et al.  Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. , 1999, The American journal of pathology.

[6]  H. Ritter,et al.  Automatic Recognition of Muscle-invasive T-lymphocytes Expressing Dipeptidyl-peptidase IV (CD26) and Analysis of the Associated Cell Surface Phenotypes , 2002 .

[7]  W. Schubert,et al.  Analyzing proteome topology and function by automated multidimensional fluorescence microscopy , 2006, Nature Biotechnology.

[8]  Walter Schubert,et al.  Toponomics and neurotoponomics: a new way to medical systems biology , 2008, Expert review of proteomics.

[9]  A. Mittag,et al.  Iterative restaining as a pivotal tool for n‐color immunophenotyping by slide‐based cytometry , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  Eugenia G. Giannopoulou,et al.  Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass spectrometry. , 2008, Journal of proteome research.

[11]  W. Schubert,et al.  Secretion and differential localization of the proteolytic cleavage products Abeta40 and Abeta42 of the Alzheimer amyloid precursor protein in human fetal myogenic cells. , 2000, European journal of cell biology.

[12]  Walter Schubert,et al.  Topological proteomics, toponomics, MELK-technology. , 2003, Advances in biochemical engineering/biotechnology.

[13]  E. Gehan,et al.  The properties of high-dimensional data spaces: implications for exploring gene and protein expression data , 2008, Nature Reviews Cancer.

[14]  Attila Tarnok,et al.  Cytomics goes 3D: Toward tissomics , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[15]  Giulio Cossu,et al.  Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs , 2006, Nature.

[16]  W. Schubert,et al.  APP+ T lymphocytes selectively sorted to endomysial tubes in polymyositis displace NCAM-expressing muscle fibers. , 1993, European journal of cell biology.

[17]  Walter Schubert,et al.  Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics , 2002 .

[18]  R. Braren,et al.  Cell-autonomous requirement for β1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice , 2008, Development.

[19]  Malfertheiner,et al.  Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+ CD18+ cells and CD8+ CD103+ cells by multi‐epitope imaging , 1998, Clinical and experimental immunology.

[20]  Walter Schubert,et al.  Fluorescence detection of protein clusters in individual cells and tissue sections by using toponome imaging system: sample preparation and measuring procedures , 2007, Nature Protocols.

[21]  M. Hemler VLA proteins in the integrin family: structures, functions, and their role on leukocytes. , 1990, Annual review of immunology.

[22]  Katie Cottingham Human Toponome Project | Human Proteinpedia is open for (free) business , 2008 .

[23]  R. Murphy,et al.  A framework for the automated analysis of subcellular patterns in human protein atlas images. , 2008, Journal of proteome research.

[24]  M. Streit,et al.  An improved method for discrimination of cell populations in tissue sections using microscopy‐based multicolor tissue cytometry , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[25]  Jianfeng Xu,et al.  Inflammation in prostate carcinogenesis , 2007, Nature Reviews Cancer.

[26]  B. Zheng,et al.  Prospective identification of myogenic endothelial cells in human skeletal muscle , 2007, Nature Biotechnology.

[27]  P. Malfertheiner,et al.  CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis* , 1998 .

[28]  Attila Tárnok,et al.  Hyperchromatic cytometry principles for cytomics using slide based cytometry , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[29]  Walter Schubert,et al.  Breaking the biological code , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[30]  W. Schubert,et al.  Antigenic determinants of T lymphocyte alpha beta receptor and other leukocyte surface proteins as differential markers of skeletal muscle regeneration: detection of spatially and timely restricted patterns by MAM microscopy. , 1992, European journal of cell biology.

[31]  Christian Stephan,et al.  Interlocking transcriptomics, proteomics and toponomics technologies for brain tissue analysis in murine hippocampus , 2008, Proteomics.