Department of Gastroenterology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200001, China.
J Exp Clin Cancer Res. 2024 Jun 6;43(1):160. doi: 10.1186/s13046-024-03082-z.
The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate.
To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction.
Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression.
In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.
四跨膜蛋白家族在迁移体的形成中起着关键作用，Tetraspanin CD151 也与肿瘤内的新生血管形成有关。然而，关于 CD151 在肝细胞癌（HCC）新生血管形成中的作用及其与迁移体的关系的研究还不够充分。
为了研究 CD151 与肝癌迁移体标志物 TSPAN4 的相关性，我们使用 HCC 患者的临床数据进行了数据库分析。评估了 HCC 组织中 CD151 的表达水平，并与患者的生存结局相关联。我们通过体外实验使用 HCC 细胞系评估了 CD151 表达对迁移体形成和细胞侵袭性的影响。使用改变 CD151 表达水平的细胞系研究迁移体的产生和体外侵袭能力。此外，通过细胞聚集实验和吞噬实验探索了迁移体的功能。随后通过 VEGF 水平分析和组织芯片实验进一步证实了 CD151 在介导迁移体参与血管生成和细胞信号转导中的作用。
我们的研究通过对临床样本的数据库分析，揭示了 CD151 表达与肝癌中迁移体标志物 TSPAN4 之间存在显著相关性。CD151 高表达与 HCC 患者的不良生存结局密切相关。实验表明，CD151 表达降低导致迁移体生成减少，体外侵袭能力减弱，体内转移潜力降低。迁移体被证明可促进细胞聚集和吞噬作用，从而促进细胞侵袭性。此外，富含 VEGF 的迁移体参与信号转导和血管生成，加速 HCC 进展。
总之，我们的研究结果支持这样一种观点，即升高的 CD151 表达促进迁移体的形成，迁移体在肝癌细胞的侵袭性和血管生成中起着关键作用，从而促进 HCC 的进展。这一发现表明，由升高的 CD151 表达产生的迁移体可能构成 HCC 抗血管生成治疗的一个有前途的高优先级靶点，为深入探索迁移体的功能和重新理解肝癌转移的机制提供了重要的见解。
