绝大多数胰腺癌患者的死亡都是由于癌细胞迅速转移到肺、肝、脑等重要器官造成的。其中，胰腺癌肝转移是胰腺癌患者死亡率高的原因之一。来自胰腺癌细胞的外泌体通常富含跨膜蛋白，用于支持肿瘤微环境的重编程和远处转移性病变的进展。我们的研究发现，由外泌体传递的跨膜糖蛋白CD44通过重编程肿瘤微环境，参与了胰腺癌的转移过程。CD44与整合素α6β4相互作用形成复合物，激活细胞内骨架蛋白及其信号通路，进而调控Src和Ras信号级联反应，促进肿瘤细胞的运动。值得注意的是，我们还证明了CD44-α6β4复合物可以通过外泌体的旁分泌作用传递到靶区。肝细胞选择性摄取具有高表达CD44的肿瘤外泌体，并通过刺激细胞因子、促炎因子和生长因子产生转移前生态位，最终支持肿瘤转移。我们的研究结果表明，外泌体CD44有可能作为胰腺癌临床诊断和治疗的生物标志物。

Rapid metastasis to vital organs such as the lung, liver, and brain is responsible for the vast majority of pancreatic cancer deaths. Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients. Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane, supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions. For the first time, our study has demonstrated that CD44, a transmembrane glycoprotein delivered by exosomes, is involved in the metastatic process of pancreatic cancer. Moreover, CD44 was found to interact with integrin α6β4 to form a complex, thereby remodeling intracellular skeleton proteins, and to promote tumor cell motility through the activation of the Src and Ras signaling cascades. Notably, we also demonstrated that the CD44–α6β4 complex can be delivered to the target region via the paracrine effects of exosomes. The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines, proinflammatory factors, and growth factors that ultimately support tumor metastasis. Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.