title: Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering.
abstract: Tumor engineering is defined as the construction of three-dimensional (3D) tumors in vitro with tissue engineering approaches. The present 3D scaffolds for tumor engineering have several limitations in terms of structure and function. To get an ideal 3D scaffold for tumor culture, A549 human pulmonary adenocarcinoma cells were implanted into immunodeficient mice to establish xenotransplatation models. Tumors were retrieved at 30-day implantation and sliced into sheets. They were subsequently decellularized by four procedures. Two decellularization methods, Tris-Trypsin-Triton multi-step treatment and sodium dodecyl sulfate (SDS) treatment, achieved complete cellular removal and thus were chosen for evaluation of histological and biochemical properties. Native tumor tissues were used as controls. Human breast cancer MCF-7 cells were cultured onto the two 3D scaffolds for further cell growth and growth factor secretion investigations, with the two-dimensional (2D) culture and cells cultured onto the Matrigel scaffolds used as controls. Results showed that Tris-Trypsin-Triton multi-step treated tumor sheets had well-preserved extracellular matrix structures and components. Their porosity was increased but elastic modulus was decreased compared with the native tumor samples. They supported MCF-7 cell repopulation and proliferation, as well as expression of growth factors. When cultured within the Tris-Trypsin-Triton treated scaffold, A549 cells and human colorectal adenocarcinoma cells (SW-480) had similar behaviors to MCF-7 cells, but human esophageal squamous cell carcinoma cells (KYSE-510) had a relatively slow cell repopulation rate. This study provides evidence that Tris-Trypsin-Triton treated acellular tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments.
authors: Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors: Wei-Dong
authors: WD
authors: Lü
authors: Department of Thoracic Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Thoracic and Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan Province, PR China.
authors: Chun-Lin
authors: CL
authors: Wu
authors: Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors: Zhi-Gang
authors: ZG
authors: Liu
authors: Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors: Guang-Yan
authors: GY
authors: Lei
authors: Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors: Jia
authors: J
authors: Liu
authors: Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors: Wei
authors: W
authors: Gao
authors: Department of Thoracic and Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan Province, PR China.
authors: Ye-Rong
authors: YR
authors: Hu
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D003094:Collagen / Q000032:analysis / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004338:Drug Combinations; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D007797:Laminin / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D016062:Porosity; D011509:Proteoglycans / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous; D014357:Trypsin / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D004338:Drug Combinations; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D012967:Sodium Dodecyl Sulfate; D003094:Collagen; D014357:Trypsin