Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research.
Martina PiccoliEdoardo D'AngeloSara CrottiFrancesca SensiLuca UrbaniEdoardo MaghinAlan BurnsPaolo De CoppiMatteo FassanMassimo RuggeFlavio RizzolioAntonio GiordanoPierluigi PilatiEnzo MammanoSalvatore PucciarelliMarco AgostiniPublished in: Journal of cellular physiology (2018)
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.
Keyphrases
- tissue engineering
- electron microscopy
- papillary thyroid
- mass spectrometry
- squamous cell
- extracellular matrix
- high resolution
- endothelial cells
- poor prognosis
- squamous cell carcinoma
- bone marrow
- oxidative stress
- high throughput
- childhood cancer
- high glucose
- ultrasound guided
- risk assessment
- young adults
- liquid chromatography
- breast reconstruction
- simultaneous determination