Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(4), P. 100528 - 100528

Published: March 12, 2023

•ECM alterations cause or accompany diseases and disorders of all organ systems.•Proteomics is a method choice to profile the composition ECM tissues.•ECM proteomics can identify novel prognostic diagnostic biomarkers.•ECM uncover proteins playing functional roles in disease etiology.•Further technical advances are needed capture diversity proteoforms The extracellular matrix (ECM) complex assembly hundreds forming architectural scaffold multicellular organisms. In addition its structural role, conveys signals orchestrating cellular phenotypes. Alterations composition, abundance, structure, mechanics have been linked affecting physiological systems, including fibrosis cancer. Deciphering protein how it changes pathophysiological contexts thus first step toward understanding health development therapeutic strategies correct disease-causing alterations. Potentially, also represents vast, yet untapped reservoir biomarkers. characterized by unique biochemical properties that hindered their study: they large, heavily uniquely posttranslationally modified, highly insoluble. Overcoming these challenges, we others devised mass-spectrometry–based proteomic approaches define "matrisome," tissues. This part this review provides historical overview research presents latest now allow profiling healthy diseased second highlights recent examples illustrating has emerged as powerful discovery pipeline cancer third discusses remaining challenges limiting our ability translate findings clinical application proposes overcome them. Lastly, introduces readers resources available facilitate interpretation datasets. was once thought be impenetrable. Mass spectrometry–based proven tool decode ECM. light progress made over past decade, there reasons believe in-depth exploration matrisome within reach may soon witness translational proteomics. organisms (1Hynes R.O. evolution metazoan matrix.J. Cell Biol. 2012; 196: 671-679Crossref PubMed Scopus (177) Google Scholar, 2Adams J.C. Extracellular evolution: an overview.in: Keeley F.W. Mecham R.P. Evolution Matrix. Springer, Berlin, Heidelberg2013: 1-25https://doi.org/10.1007/978-3-642-36002-2_1Crossref 3Karamanos N.K. Theocharis A.D. Piperigkou Z. Manou D. Passi A. Skandalis S.S. et al.A guide functions matrix.FEBS J. 2021; 288: 6850-6912Crossref (34) Scholar). As such, guides cell polarization serves substrate migration, organizes cells into tissues organs, confers mechanical roles, exerts signaling through mechanotransduction (4Humphrey J.D. Dufresne E.R. Schwartz M.A. Mechanotransduction homeostasis.Nat. Rev. Mol. 2014; 15: 802-812Crossref (1185) 5Dooling L.J. Saini K. Anlaş A.A. Discher D.E. Tissue coevolves with fibrillar matrisomes fibrotic tissues.Matrix 2022; 111: 153-188Crossref (0) It cues interpreted via cell-surface receptors (e.g., integrins (6Kanchanawong P. Calderwood D.A. Organization, dynamics mechanoregulation integrin-mediated cell–ECM adhesions.Nat. 24: 142-161Crossref (7) Scholar), syndecans, adhesion GPCRs (7Liebscher I. Cevheroğlu O. Hsiao C.C. Maia A.F. Schihada H. Scholz N. GPCR research.FEBS 289: 7610-7630Crossref (5) Scholar)) orchestrate most, if not all, functions, from proliferation survival stemness differentiation. plays critical during development, growth, other processes wound healing aging (8Yamada K.M. Collins J.W. Cruz Walma Doyle Morales S.G. Lu al.Extracellular invasion tissue morphogenesis.Int. Exp. Pathol. 2019; 100: 144-152Crossref (47) 9Dzamba B.J. DeSimone D.W. sculpting embryonic tissues.Curr. Top Dev. 2018; 130: 245-274Crossref (49) 10Karamanos Neill T. Iozzo R.V. Matrix modeling remodeling: biological interplay regulating homeostasis diseases.Matrix 75–76: 1-11Crossref (156) 11Lausecker F. Lennon R. Randles M.J. kidney health, aging, disease.Kidney Int. 102: 1000-1012Abstract Full Text PDF (1) 12Ewald C.Y. longevity: systems-level approach defining matreotypes promoting aging.Gerontology. 2020; 66: 266-274Crossref (31) Simply put, essential for life. dynamic compartment undergoes compositional turnover remodeling mediated both enzymatic nonenzymatic processes. Disruption homeostasis, caused mutations genes (13Lamandé S.R. Bateman J.F. Genetic matrix.Anat. Rec. (Hoboken). 303: 1527-1542Crossref imbalance between production degradation, inadequate remodeling, results systems (14Lu Takai Weaver V.M. Werb degradation disease.Cold Spring Harb. Perspect. 2011; 3: a005058Crossref (1375) 15Bonnans C. Chou Remodelling disease.Nat. 786-801Crossref (2349) 16Theocharis Karamanos multitasking player disease.FEBS 286: 2830-2869Crossref (190) Scholar) musculoskeletal system Ehlers–Danlos syndrome (17Malfait Castori M. Francomano C.A. Giunta Kosho Byers P.H. Ehlers-Danlos syndromes.Nat. Dis. Primers. 6: 64Crossref (82) arthritis), skin scleroderma (18Schulz J.N. Plomann Sengle G. Gullberg Krieg Eckes B. New developments on - emanating control myofibroblasts.Matrix 68–69: 522-532Crossref (48) epidermolysis bullosa (19Bruckner-Tuderman L. Has Disorders cutaneous basement membrane zone--the paradigm bullosa.Matrix 33: 29-34Crossref Scholar)), cardiovascular Marfan (20Cook J.R. Carta Galatioto Ramirez Cardiovascular manifestations related diseases; multiple causing similar phenotypes.Clin. Genet. 2015; 87: 11-20Crossref (52) respiratory (lung (21Zhou Y. Horowitz Naba Ambalavanan Atabai Balestrini lung disease.Matrix 73: 77-104Crossref (138) excretory Alport syndrome, Goodpasture renal (22Bülow R.D. Boor fibrosis: more than just scaffold.J. Histochem. Cytochem. 67: 643-661Crossref (134) 23Chew Basement defects genetic diseases.Front. Pediatr. 11Crossref (50) list few. addition, excessive accumulation hallmark (24Pakshir Hinz big five macrophages, myofibroblasts, matrix, mechanics, miscommunication.Matrix 81-93Crossref (211) (25Pickup M.W. Mouw J.K. modulates hallmarks cancer.EMBO Rep. 1243-1253Crossref (1078) 26Cox T.R. cancer.Nat. Cancer. 21: 217-238Crossref (222) 27Winkler Abisoye-Ogunniyan Metcalf K.J. Concepts remodelling tumour progression metastasis.Nat. Commun. 11: 5120Crossref (584) extent deposition context cancer, assessed tumor:stroma ratio, shown value patients colorectal (28Souza da Silva R.M. Queiroga E.M. Paz A.R. Neves F.F.P. Cunha K.S. Dias E.P. Standardized assessment tumor-stroma ratio cancer: interobserver validation reproducibility potential factor.Clin. 14https://doi.org/10.1177/2632010X21989686Crossref 29van Pelt G.W. Sandberg T.P. Morreau Gelderblom van Krieken J.H.J.M. Tollenaar R.A.E.M. al.The tumour-stroma colon role impact.Histopathology. 197-206Crossref Nine 70-gene MammaPrint panel used early breast diagnosis (30Cardoso van't Veer Bogaerts Slaets Viale Delaloge S. al.70-Gene signature aid treatment decisions early-stage cancer.N. Engl. Med. 2016; 375: 717-729Crossref genes. present advantage being readily accessible, outside cells. Consequently, targeted delivery imaging agents (31Jailkhani Ingram Rashidian Rickelt Tian Mak al.Noninvasive tumor progression, metastasis, using nanobody targeting matrix.Proc. Nat. Acad. Sci. U. 116: 14181-14190Crossref 32Santimaria Moscatelli G.L. Giovannoni Neri Viti al.Immunoscintigraphic detection ED-B domain fibronectin, marker angiogenesis, cancer.Clin. Cancer Res. 2003; 9: 571-579PubMed 33Steiner Antibody-radionuclide conjugates therapy: considerations new trends.Clin. 17: 6406-6416Crossref (125) drugs, example, bispecific composed moiety recognizing disease-specific immunomodulatory cytokine (34Pasche Immunocytokines: class potent armed antibodies.Drug Discov. Today. 583-590Crossref (129) 35Lieverse R.I.Y. Van Limbergen E.J. Oberije C.J.G. Troost E.G.C. Hadrup Dingemans A.M.C. al.Stereotactic ablative body radiotherapy (SABR) combined immunotherapy (L19-IL2) versus standard care stage IV NSCLC patients, ImmunoSABR: multicentre, randomised controlled open-label phase II trial.BMC 20: 557Crossref 36Momin Mehta Bennett N.R. Ma Palmeri Chinn M.M. al.Anchoring intratumorally administered cytokines collagen safely potentiates systemic immunotherapy.Sci. Transl. 11eaaw2614Crossref (98) proposed modulating architecture biophysical ECM–cell interactions could valid various (37Nyström Bernasconi Bornert Therapies skin.Matrix 71–72: 330-347Crossref (18) 38Schuppan Ashfaq-Khan Yang A.T. Kim Y.O. Liver direct antifibrotic therapies.Matrix 435-451Crossref (244) 39Bejarano Jordāo M.J.C. Joyce J.A. Therapeutic microenvironment.Cancer 933-959Crossref (274) 40Hauge Rofstad E.K. Antifibrotic therapy normalize microenvironment.J. 18: 207Crossref (40) 41Lampi M.C. Reinhart-King Targeting stiffness attenuate disease: molecular mechanisms trials.Sci. 10eaao0475Crossref (279) 42Ley Rivera-Nieves Sandborn W.J. Shattil Integrin-based therapeutics: basis, use drugs.Nat. Drug 173-183Crossref (273) constitutes large biomarkers targets. Yet, while some elastin) families collagens, tenascins) extensively studied, whole, remained, until recently, largely underexplored (43Wilson matrix: but important proteome.Expert Proteomics. 2010; 7: 803-806Crossref (14) uncharted (44Filipe E.C. Chitty J.L. Cox Charting unexplored cancer.Int. 99: 58-76Crossref very allowing assemble capable withstanding significant stress deformations study global core, tend average 1045 amino acids long. undergo extensive intracellular posttranslational modifications (PTMs), glycosylation, lysine proline hydroxylation collagens collagen-domain-containing contribute stabilization triple-helical structure (45Rappu Salo A.M. Myllyharju Heino Role prolyl collagens.Essays Biochem. 63: 325-335Crossref glycation. higher-order structures established hydrogen bonds (46Buehler Nature designs tough collagen: explaining nanostructure fibrils.Proc. Natl. 2006; 103: 12285-12290Crossref (593) 47Shoulders M.D. Raines R.T. Collagen stability.Annu. 2009; 78: 929-958Crossref (2243) disulfide fibronectin dimers (48Schwarzbauer J.E. Fibronectins, fibrillogenesis, vivo functions.Cold 2011 Jul 1; a005041Crossref (280) covalent cross-links elastin (49Ozsvar Cain S.A. Baldock Tarakanova Weiss A.S. Tropoelastin assembly.Front. Bioeng. Biotechnol. 9643110Crossref (35) (50Ricard-Blum family.Cold a004978Crossref (1080) Scholar)). These making insoluble and, hence, challenging like SDS-PAGE, immunoprecipitation pull-down assays mass spectrometry (MS). Because high insolubility, underrepresented Further contributing underrepresentation fact that, apart few exceptions, small fraction mass. challenge comprehensive characterization broad range terms abundance. comprised abundant components, which generate many peptides (for 121 trypsin cleavage sites alpha 1 chain I), smaller secreted factors, such ECM-remodeling enzymes, growth morphogens, much lower limitation ECM, instrumentations methods fractionate peptide samples, will discussed here, key complexity different subproteomes applied (see below). attempts at ECM-rich tissues, cartilage, following enrichment employed SDS-PAGE 2D gel electrophoresis separate subsets solubilized, followed liquid chromatography coupled tandem (LC-MS/MS). studies reported up dozen proteins. At time, no feat instrumental helping shape field (51Wilson Cartilage proteomics: solutions advances.Proteomics Clin. Appl. 2008; 2: 251-263Crossref 52Lammi Häyrinen Mahonen Proteomic analysis cartilage- bone-associated samples.Electrophoresis. 27: 2687-2701Crossref 53Hattar Maller McDaniel Hansen K.C. Hedman Lyons al.Tamoxifen induces pleiotrophic mammary stroma resulting suppresses transformed phenotypes.Breast R5Crossref (53) 54Wilson Diseberg Gordon Zivkovic Tatarczuch Mackie al.Comprehensive cartilage formation maturation sequential extraction label-free quantitative proteomics.Mol. 1296-1313Abstract (63) 55Belluoccio Wilson Thornton D.J. Wallis Gorman J.J. mouse plate cartilage.Proteomics. 6549-6553Crossref (30) 56Hansen Kiemele O'Brien Shankar Fornetti al.An in-solution ultrasonication-assisted digestion improved proteome coverage.Mol. 8: 1648-1657Abstract (85) Of note, sample preparation protocols tailored account posed (insolubility, glycosylation), separation 1D resulted identification nearly 100 distinct (57Didangelos Yin X. Mandal Baumert Jahangiri Mayr Proteomics space components human aorta.Mol. 2048-2062Abstract (214) 58Didangelos Saje Smith Xu Q. abdominal aortic aneurysms: approach.Mol. 10https://doi.org/10.1074/mcp.M111.008128Abstract (146) However, most studies, known proteins, expected detected those were identified. One then ask: ensure capturing tissues? And indeed, faced when attempting characterize, unbiased manner, lack defined parts systematically annotate experimental output. result, days proteomics, listed "ECM" involved adhesions incorporated Conversely, prior knowledge existed would fail annotated belonging represented any attempt aiming states. became obvious analytical decipher discuss enhancement purpose biomarker target focus Special Issue Clinical Proteomics, article highlight selected performed samples rodent models show promise. organisms, zebrafish (59Chen W.C.W. Wang Missinato Park Long Liu H.J. al.Decellularized cardiac mammalian heart regeneration.Sci. Adv. 2e1600844Crossref (83) 60Garcia-Puig Mosquera Jiménez-Delgado García-Pastor Jorba Navajas al.Proteomics regeneration.Mol. 1745-1755Abstract 61Kessels M.Y. Huitema L.F.A. Boeren Kranenbarg Schulte-Merker Leeuwen JL skeletal matrix.PLoS One. 9e90568Crossref (32) drosophila (62Sessions A.O. Kaushik Parker Raedschelders Bodmer Eyk downregulation Drosophila preserves contractile function improves lifespan.Matrix 2017; 62: 15-27Crossref (15) planarians (63Sonpho E. Mann F.G. Levy Ross Guerrero-Hernández Florens al.Decellularization Enables planarian 20100137Abstract produced culture. advance fundamental disease. bottom-up MS-based but, worth noting modalities facets glycosylation patterns glycomics (64Raghunathan Sethi M.K. Klein Zaia glycomics, glycoproteomics molecules.Mol. 2138-2148Abstract (29) 65de Haan Pučić-Baković Novokmet Falck Lageveen-Kammeijer Razdorov al.Developments perspectives high-throughput glycomics: enabling thousands samples.Glycobiology. 32: 651-663Crossref 66Kellman B.P. Lewis N.E. Big-data tools connect glycan biosynthesis communication.Trends 46: 284-300Abstract (23) 67Riley N.M. Bertozzi C.R. Pitteri S.J. A pragmatic spectrometry-based glycoproteomics.Mol. 20100029Abstract fragments degradomics (68Haack Overall C.M. auf dem Keller Degradomics technologies exploration.Matrix 114: 1-17Crossref localization distribution MS (69Angel P.M. Comte-Walters Ball L.E. Talbot Brockbank K.G.M. al.Mapping formalin-fixed, paraffin-embedded MALDI spectrometry.J. Proteome 635-646Crossref (51) 70Clift C.L. Drake R.R. Angel Multiplexed serial enzyme digests formalin-fixed sections.Anal. Bioanal. Chem. 413: 2709-2719Crossref (8) 2012, published journal describing two-pronged (71Naba Clauser K.R. Hoersch Carr Hynes matrisome: silico definition normal matrices.Mol. 11https://doi.org/10.1074/mcp.M111.014647Abstract (668) While had attempted limitations described above decellularizing extracting guanidine hydrochloride), set tackle them all. brief, took differential solubility deplete non-ECM incubations extraction, decellularization, buffers concomitantly enriching Observing incubation 8 M urea mM DTT did fully solubilize ECM-enriched suspecting found material, processed "crude" M-urea-resuspended samples. We hypothesized deglycosylating enhance accessibility treated Peptide-N-glycosidase F (PNGaseF). further preincubated deglycosylated suspension LysC, protease digesting tightly folded tryptic digestion. To fractionated off-gel electrophoresis. Last, quantification stipulated ECM-specific PTMs hydroxylations variable database search. Indeed, 19% acid sequence I positions X Y X-Y-Gly repeats often hydroxylated parallel, developed robust nomenclature classify characteristic domain-based organization (72Hohenester Eng

Language: Английский