title: Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion.
abstract: In the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation. We analyzed the 3D structure, geometrical measurements and anisotropy of the ECM isolated from (i) human bladder mucosa (basal lamina and lamina propria) and muscularis propria; and, (ii) bladder carcinoma (BC). Next, binding and invasion of bladder metastatic cell line was observed on synthetic scaffold recapitulating anisotropy of tumoral ECM, but not on scaffold with disorganized texture typical of non-neoplastic lamina propria. This study provided information regarding the ultrastructure and geometry of healthy human bladder and BC ECMs. Likewise, using synthetic scaffolds we identified linearization of the texture as a mandatory feature for BC cell invasion. Integrating microstructure and geometry with biochemical and mechanical factors could support the development of an innovative synthetic bladder substitute or a tumoral scaffold predictive of chemotherapy outcomes.
authors: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Massimo
authors: M
authors: Alfano
authors: Pathology Unit, Department of Biomedical and Clinical Sciences, L. Sacco Hospital, Università degli Studi di Milano, Milan, Italy.
authors: Manuela
authors: M
authors: Nebuloni
authors: Centro di Microscopia Elettronica per lo studio delle Nanotecnologie Applicate alla medicina "C.M.E.N.A.", Department of Biomedical and Clinical Sciences, L. Sacco Hospital, Università degli Studi di Milano, Milan, Italy.
authors: Raffaele
authors: R
authors: Allevi
authors: Pathology Unit, Department of Biomedical and Clinical Sciences, L. Sacco Hospital, Università degli Studi di Milano, Milan, Italy.
authors: Pietro
authors: P
authors: Zerbi
authors: Pathology Unit, Department of Biomedical and Clinical Sciences, L. Sacco Hospital, Università degli Studi di Milano, Milan, Italy.
authors: Erika
authors: E
authors: Longhi
authors: Pathology Unit, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Roberta
authors: R
authors: Lucianò
authors: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Irene
authors: I
authors: Locatelli
authors: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Angela
authors: A
authors: Pecoraro
authors: Fondazione Filarete, viale Ortles 22/4, 21033, Milan, Italy.
authors: Marco
authors: M
authors: Indrieri
authors: Fondazione Filarete, viale Ortles 22/4, 21033, Milan, Italy.
authors: Chantal
authors: C
authors: Speziali
authors: Pathology Unit, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors: Claudio
authors: C
authors: Doglioni
authors: Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) and Dept. of Physics, Università degli Studi di Milano, Milan, Italy.
authors: Paolo
authors: P
authors: Milani
authors: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors: Francesco
authors: F
authors: Montorsi
authors: Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors: Andrea
authors: A
authors: Salonia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005109:Extracellular Matrix / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology*; D059016:Tumor Microenvironment; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology*