Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology

Autor: Estelle Collin, Ying Liu, Sara Trabulo, Rita T. Lawlor, Diana Behrens, David Osuna de la Peña, Daniela Loessner, Marianthi Tatari, Christopher Heeschen, Aldo Scarpa, Shreya Sharma, Mert Erkan, Alvaro Mata
Přispěvatelé: Erkan, Murat Mert (ORCID 0000-0002-2753-0234 & YÖK ID 214689), de la Pena, Osuna D., Trabulo, S.M.D., Collin, E., Liu, Y., Sharma, S., Tatari, M., Behrens, D., Lawlor, R.T., Scarpa, A., Heeschen, C., Mata, A., Loessner, D., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cancer microenvironment
EXPRESSION
STEM-CELL
STELLATE CELLS
BIOMATERIALS
VITRO
EXPRESSION
PHENOTYPES
HYDROGELS
PLATFORM
COLLAGEN
PROMOTE
STELLATE CELLS
Stromal cell
Science
HYDROGELS
Cell Culture Techniques
General Physics and Astronomy
Bioengineering
PHENOTYPES
Biology
Models
Biological
General Biochemistry
Genetics and Molecular Biology
Article
Extracellular matrix
In vivo
Cancer stem cell
Pancreatic cancer
medicine
Tumor Cells
Cultured
Humans
PROMOTE
VITRO
Cancer models
BIOMATERIALS
Science and technology
Multidisciplinary
Cancer stem cells
Gene Expression Profiling
Reproducibility of Results
PLATFORM
General Chemistry
medicine.disease
Precision medicine
Peptide
Cell culture techniques
Gene expression profiling
Gene expression regulation
Neoplastic stem cells
Pancreatic neoplasms
Reproducibility of results
Stromal cells
COLLAGEN
STEM-CELL
Gene Expression Regulation
Neoplastic
Pancreatic Neoplasms
Cancer research
Neoplastic Stem Cells
Stem cell
Stromal Cells
Ex vivo
Carcinoma
Pancreatic Ductal
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)
Nature Communications
ISSN: 2041-1723
Popis: Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.
Biotechnology and Biological Sciences Research Council; LIDo Grant; Medical Research Council; UK Regenerative Medicine Platform Acellular/Smart Materials-3D Architecture; Fondazione Italiana Malattie Pancreas; Italian Ministry of Health; Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi”; European Union (EU); Horizon 2020; European Community Seventh Framework Programme; FP7/2007-2013; CAM-PaC Consortium; BIOMORPH; Marie Curie Integration Grant; STROFUNSCAFF; ERC Starting Grant; Associazione Italiana Ricerca Cancro; Barts Cancer Institute Catalyst; IMPETUS Awards
Databáze: OpenAIRE
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