title: Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.
abstract: The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential.
authors.affiliation: L. Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.affiliation: Department of Pathology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Albarello
authors.affiliation: ProMiFa, Protein Microsequencing Facility, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Annapaola
authors.initials: A
authors.lastname: Andolfo
authors.affiliation: ProMiFa, Protein Microsequencing Facility, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Magagnotti
authors.affiliation: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Genovese
authors.affiliation: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Locatelli
authors.affiliation: Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tonon
authors.affiliation: L. Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Longhi
authors.affiliation: L. Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Zerbi
authors.affiliation: L. Sacco Hospital, Department of Biomedical and Clinical Sciences, Centro di Microscopia Elettronica per lo studio delle Nanotecnologie Applicate alla medicina "C.M.E.N.A.", University of Milan, 20157 Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Allevi
authors.affiliation: Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) and Dept. of Physics, Università degli Studi di Milano, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Podestà
authors.affiliation: Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) and Dept. of Physics, Università degli Studi di Milano, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Puricelli
authors.affiliation: Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) and Dept. of Physics, Università degli Studi di Milano, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Milani
authors.affiliation: Diagnostica e Ricerca San Raffaele, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Soldarini
authors.affiliation: Università Vita-Salute San Raffaele, 20132 Milan, Italy.|Research Doctorate Program in Urology, Magna Graecia University, 88100 Catanzaro, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salonia
authors.affiliation: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Alfano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D003094:Collagen; D008249:Protein-Lysine 6-Oxidase