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Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research
Author(s) -
Piccoli Martina,
D'Angelo Edoardo,
Crotti Sara,
Sensi Francesca,
Urbani Luca,
Maghin Edoardo,
Burns Alan,
De Coppi Paolo,
Fassan Matteo,
Rugge Massimo,
Rizzolio Flavio,
Giordano Antonio,
Pilati Pierluigi,
Mammano Enzo,
Pucciarelli Salvatore,
Agostini Marco
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26403
Subject(s) - decellularization , stromal cell , colorectal cancer , 3d cell culture , in vitro , cancer , immunohistochemistry , tumor microenvironment , cancer research , extracellular matrix , biology , pathology , chemistry , microbiology and biotechnology , medicine , biochemistry , tumor cells , genetics
Three‐dimensional (3D) cancer models are overlooking the scientific landscape with the primary goal of bridging the gaps between two‐dimensional (2D) cell lines, animal models and clinical research. Here, we describe an innovative tissue engineering approach applied to colorectal cancer (CRC) starting from decellularized human biopsies in order to generate an organotypic 3D‐bioactive model. This in vitro 3D system recapitulates the ultrastructural environment of native tissue as demonstrated by histology, immunohistochemistry, immunofluorescence and scanning electron microscopy analyses. Mass spectrometry of proteome and secretome confirmed a different stromal composition between decellularized healthy mucosa and CRC in terms of structural and secreted proteins. Importantly, we proved that our 3D acellular matrices retained their biological properties: using CAM assay, we observed a decreased angiogenic potential in decellularized CRC compared with healthy tissue, caused by direct effect of DEFA3. We demonstrated that following a 5 days of recellularization with HT‐29 cell line, the 3D tumor matrices induced an over‐expression of IL‐8 , a DEFA3‐mediated pathway and a mandatory chemokine in cancer growth and proliferation. Given the biological activity maintained by the scaffolds after decellularization, we believe this approach is a powerful tool for future pre‐clinical research and screenings.