title: To the novel paradigm of proteome-based cell therapy of tumors: through comparative proteome mapping of tumor stem cells and tissue-specific stem cells of humans.
abstract: We performed proteome mapping (PM), cataloging, and bioinformation analysis of protein lysates of human neural (CD133(+)) progenitor and stem cells (NPSCs) isolated from the olfactory sheath of a nose, multipotent mesenchymal (CD29(+), CD44(+), CD73(+), CD90(+), CD34(-)) stromal cells (MMSCs) isolated from human bone marrow, and tumor (CD133(+)) stem cells (TSCs) isolated from the human U87 glioblastoma (GB) cell line. We identified 1,664 proteins in the examined lysates of stem cells (SCs), 1,052 (63.2%) of which are identical in NPSCs and TSCs and 607 proteins (36.47%) of which are identical in MMSCs and TSCs. Other proteins in U87 GB TSCs are oncospecific or carcinogenesis associated. The biological processes, molecular functions, cell localization, and protein signal pathways of the proteins available in all three proteomes were annotated by PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), PANTHER (http://www.pantherdb.org/), GeneOntology (http://www.geneontology.org/), and KEGG (http://www.genome.jp/kegg/) databases. It was shown that gliomaspheres of U87 GB had only 10 intracellular signal transduction pathways (ISTP) that were not modified by the neoplastic process, but only two of them (integrin and focal adhesion pathways) were accessible for regulatory action on gene candidates in the TSC nucleus. Carcinogenesis-free membrane proteins, IPST, and genes expressing proteins of these pathways in U87 GB TSCs can be viewed as main targets for regulatory effects on TSCs. We offer a novel concept of proteome-based complex therapy of tumors. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
authors.affiliation: Federal Research Center for Specialized Types of Medical Assistance and Medical Technologies of FMBA of Russia, Moscow, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Bryukhovetskiy
authors.forename: Valeriy
authors.initials: V
authors.lastname: Shevchenko
authors.forename: Sergey
authors.initials: S
authors.lastname: Kovalev
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chekhonin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Baklaushev
authors.forename: Igor
authors.initials: I
authors.lastname: Bryukhovetskiy
authors.forename: Maria
authors.initials: M
authors.lastname: Zhukova
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction; D033581:Stem Cell Transplantation
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; D020543:Proteome