Pancreatic cancer (PC) is an aggressive and fatal malignant tumor, and exosomes have been reported to be closely related to PC invasion and metastasis. Here we found that Exo70, a key subunit of the exocyst complex, promoted PC metastasis by regulating the secretion of tumor exosomes. Clinical sample studies showed that Exo70 was highly expressed in PC and negatively correlated with patients’ survival. Exo70 promoted PC cell lines’ invasion and migration. Interestingly, knockdown of Exo70, or using an Exo70 inhibitor (ES2) inhibited the secretion of tumor exosomes and increased the accumulation of cellular vesicles. Furthermore, Exo70 was found to accumulate in the exosomes, which then fused with neighboring PC cells and promoted their invasion. Moreover, Exo70 increased the expression of exosomal PD-L1, leading to the immune escape of PC cells. In vivo, knockdown of Exo70 or treatment with ES2 both decreased the tumor metastasis of PC cells in mice. This study provides new insight into the mechanism of invasion and metastasis in PC and identifies Exo70 as a potential prognostic factor and therapeutic target for PC.
胰腺癌是一种侵袭性强且致命的恶性肿瘤，已有研究表明外泌体与胰腺癌的侵袭和转移密切相关。本研究发现，外泌体复合物的关键亚基Exo70通过调控肿瘤外泌体的分泌促进胰腺癌转移。临床样本分析显示，Exo70在胰腺癌中高表达，且与患者生存率呈负相关。Exo70能够促进胰腺癌细胞系的侵袭和迁移能力。值得注意的是，敲低Exo70或使用Exo70抑制剂（ES2）可抑制肿瘤外泌体的分泌，并导致细胞内囊泡积累。进一步研究发现，Exo70在外泌体中富集，这些外泌体可与邻近胰腺癌细胞融合并促进其侵袭。此外，Exo70还能增加外泌体PD-L1的表达，从而介导胰腺癌细胞的免疫逃逸。在体内实验中，敲低Exo70或使用ES2处理均能显著抑制小鼠模型中胰腺癌细胞的转移。本研究为胰腺癌侵袭转移机制提供了新见解，并证实Exo70可作为胰腺癌潜在的预后标志物和治疗靶点。
Exo70 Promotes the Invasion of Pancreatic Cancer Cells via the Regulation of Exosomes
肿瘤(癌症)患者之家