Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin–integrin α₃/α₆ signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness—a hallmark of pancreatic cancer—was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro.

捕捉人类肿瘤病理生理特征的体外实验模型对于基础和转化癌症生物学至关重要。在这里，我们描述了一种完全合成的水凝胶细胞外基质，旨在引发培养中胰腺环境的关键表型特征。为了使基因工程小鼠模型和人类患者的正常和癌性胰腺类器官能够生长，在水凝胶支架中根据经验定义和复制了基本的粘附线索，揭示了层粘连蛋白-整合素 α ₃ /α _{6的功能作用}在胰腺类器官的建立和存活中发出信号。改变的组织硬度——胰腺癌的一个标志——通过调整水凝胶的特性以参与机械传感途径并改变类器官的生长，在培养中得到了概括。胰腺基质细胞很容易掺入水凝胶中，并在体内复制了肿瘤环境特征的表型特征。因此，该模型概括了病理重塑的肿瘤微环境，用于体外研究正常和胰腺癌细胞。