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Collagen Lattice Model, Populated with Heterogeneous Cancer-Associated Fibroblasts, Facilitates Advanced Reconstruction of Pancreatic Cancer Microenvironment.
Song, Xiaoyu; Nihashi, Yuma; Imai, Yukiko; Mori, Nobuhito; Kagaya, Noritaka; Suenaga, Hikaru; Shin-Ya, Kazuo; Yamamoto, Masamichi; Setoyama, Daiki; Kunisaki, Yuya; Kida, Yasuyuki S.
Afiliação
  • Song X; Tsukuba Life Science Innovation Program (T-LSI), School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8572, Japan.
  • Nihashi Y; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Imai Y; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Mori N; Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
  • Kagaya N; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Suenaga H; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Shin-Ya K; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Yamamoto M; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan.
  • Setoyama D; Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, Ki-shibe-Shimmachi, Suita 564-8565, Japan.
  • Kunisaki Y; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan.
  • Kida YS; Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Int J Mol Sci ; 25(7)2024 Mar 27.
Article em En | MEDLINE | ID: mdl-38612551
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a solid-tumor malignancy. To enhance the treatment landscape of PDAC, a 3D model optimized for rigorous drug screening is essential. Within the PDAC tumor microenvironment, a dense stroma comprising a large extracellular matrix and cancer-associated fibroblasts (CAFs) is well-known for its vital role in modulating tumor growth, cellular heterogeneity, bidirectional paracrine signaling, and chemoresistance. In this study, we employed a fibroblast-populated collagen lattice (FPCL) modeling approach that has the ability to replicate fibroblast contractility in the collagenous matrix to build dense stroma. This FPCL model allows CAF differentiation by facilitating multifaceted cell-cell interactions between cancer cells and CAFs, with the differentiation further influenced by mechanical forces and hypoxia carried within the 3D structure. Our FPCL models displayed hallmark features, including ductal gland structures and differentiated CAFs with spindle shapes. Through morphological explorations alongside in-depth transcriptomic and metabolomic profiling, we identified substantial molecular shifts from the nascent to mature model stages and potential metabolic biomarkers, such as proline. The initial pharmacological assays highlighted the effectiveness of our FPCL model in screening for improved therapeutic strategies. In conclusion, our PDAC modeling platform mirrors complex tumor microenvironmental dynamics and offers an unparalleled perspective for therapeutic exploration.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Fibroblastos Associados a Câncer Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Fibroblastos Associados a Câncer Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão