title: 3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus.
abstract: Interactions between malignant and stromal cells and the 3D spatial architecture of the tumor both substantially modify tumor behavior, including the responses to small molecule drugs and biological therapies. Conventional 2D culture systems cannot replicate this complexity. To overcome these limitations and more accurately model solid tumors, we developed a highly versatile 3D PEG-fibrin hydrogel model of human lung adenocarcinoma. Our model relevantly recapitulates the effect of oncolytic adenovirus; tumor responses in this setting nearly reproduce those observed in vivo. We have also validated the use of this model for complex, long-term, 3D cultures of cancer cells and their stroma (fibroblasts and endothelial cells). Both tumor proliferation and invasiveness were enhanced in the presence of stromal components. These results validate our 3D hydrogel model as a relevant platform to study cancer biology and tumor responses to biological treatments.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA; Hematology/Oncology Department, Bambino Gesù Children's Hospital, Rome, Italy. Electronic address: francesca.delbufalo@opbg.net.
authors.forename: Francesca
authors.initials: F
authors.lastname: Del Bufalo
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Manzo
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Hoyos
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yagyu
authors.affiliation: Hematology/Oncology Department, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Caruana
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA; Congenital Heart Surgery Services, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jacot
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Benavides
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosen
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D016513:Mice, SCID; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D050504:Oncolytic Viruses / Q000187:drug effects / Q000502:physiology*; D009940:Organoids; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005337:Fibrin
keywords: 3D tumor model; Oncolytic adenovirus; Preclinical drug testing; Tumor microenvironment