Department of Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.
Int J Mol Sci. 2023 Aug 20;24(16):12993. doi: 10.3390/ijms241612993.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer with a poor prognosis and low survival rates. The prognostic and predictive biomarkers of PDAC are still largely unknown. The receptor CD74 was recently identified as a regulator of oncogenic properties in various cancers. However, the precise molecular mechanism of CD74 action in PDAC remains little understood. We investigated the role of CD74 by silencing CD74 in the pancreatic cancer cell line Capan-1. CD74 knockdown led to reductions in cell proliferation, migration, and invasion and increased apoptosis. Moreover, silencing CD74 resulted in the decreased expression and secretion of S100A8 and S100A9. An indirect co-culture of fibroblasts and tumor cells revealed that fibroblasts exposed to conditioned media from CD74 knockdown cells exhibited a reduced expression of inflammatory cytokines, suggesting a role of CD74 in influencing cytokine secretion in the tumor microenvironment. Overall, our study provides valuable insights into the critical role of CD74 in regulating the oncogenic properties of pancreatic cancer cells and its influence on the expression and secretion of S100A8 and S100A9. Taken together, these findings indicate CD74 as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.
胰腺导管腺癌 (PDAC) 是一种侵袭性胰腺癌，预后不良，生存率低。PDAC 的预后和预测生物标志物在很大程度上仍然未知。受体 CD74 最近被确定为各种癌症中致癌特性的调节剂。然而，CD74 在 PDAC 中的作用的确切分子机制仍知之甚少。我们通过在胰腺癌细胞系 Capan-1 中沉默 CD74 来研究 CD74 的作用。CD74 敲低导致细胞增殖、迁移和侵袭减少，凋亡增加。此外，沉默 CD74 导致 S100A8 和 S100A9 的表达和分泌减少。成纤维细胞和肿瘤细胞的间接共培养表明，暴露于 CD74 敲低细胞条件培养基的成纤维细胞表现出炎症细胞因子表达减少，表明 CD74 在影响肿瘤微环境中细胞因子分泌方面发挥作用。总的来说，我们的研究提供了有价值的见解，即 CD74 在调节胰腺癌细胞的致癌特性及其对 S100A8 和 S100A9 的表达和分泌的影响方面具有重要作用。综上所述，这些发现表明 CD74 是一种潜在的诊断生物标志物和治疗靶点，可用于治疗胰腺癌。
