细胞外基质
肿瘤微环境
自愈水凝胶
胰腺癌
体内
癌症研究
上皮-间质转换
化学
癌细胞
癌症
细胞生物学
生物物理学
材料科学
医学
肿瘤细胞
生物
内科学
转移
生物技术
有机化学
作者
Ying Liu,Babatunde O. Okesola,David Osuna de la Peña,Weiqi Li,Meng‐Lay Lin,Sara Trabulo,Marianthi Tatari,Rita T. Lawlor,Aldo Scarpa,Wen Wang,Martin M. Knight,Daniela Loessner,Christopher Heeschen,Álvaro Mata,Oliver M.T. Pearce
标识
DOI:10.1002/adhm.202301941
摘要
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression and therapy resistance. To further our understanding of how stiffening of the tumor microenvironment (TME) contributes to aggressiveness, we develop a three‐dimensional (3D) self‐assembling hydrogel disease model based on peptide amphiphiles (PAs, PA‐E3Y ) designed to tailor stiffness. The model displays nanofibrous architectures reminiscent of native TME and enables the study of the invasive behavior of PDAC cells. We demonstrate enhanced tuneability of stiffness by interacting thermally annealed aqueous solutions of PA‐E3Y (PA‐E3Y h ) with divalent cations to create hydrogels with mechanical properties and ultrastructure similar to native tumor ECM. We show that stiffening of PA‐E3Y h hydrogels to levels found in PDAC induces ECM deposition, promotes epithelial‐to‐mesenchymal transition, enriches for CD133 + /CXCR4 + cancer stem cells, and subsequently enhances drug resistance. Our findings reveal how a stiff 3D environment renders PDAC cells more aggressive and therefore more faithfully recapitulates in vivo tumors. This article is protected by copyright. All rights reserved
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