Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

Martina Piccoli, Edoardo D'Angelo, Sara Crotti, Francesca Sensi, Luca Urbani, Edoardo Maghin, Alan Burns, Paolo De Coppi, Matteo Fassan, Massimo Rugge, Flavio Rizzolio, Antonio Giordano, Pierluigi Pilati, Enzo Mammano, Salvatore Pucciarelli, Marco Agostini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)5937-5948
Number of pages12
JournalJournal of Cellular Physiology
Volume233
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Keywords

  • 3D in vitro culture
  • biological scaffold
  • colorectal cancer
  • extracellular matrix
  • tumor microenvironment

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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