General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124, Pisa, Italy.
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124, Pisa, Italy.
Pancreatology. 2020 Sep;20(6):1218-1225. doi: 10.1016/j.pan.2020.08.004. Epub 2020 Aug 11.
Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.
Samples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.
All cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.
Our work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.
在理解胰腺导管腺癌 (PDAC) 生物学的几个新靶点中，朊病毒蛋白 (PrPc) 值得特别提及，因为它们具有明显的神经趋向性。实际上，PrPc 可能在肿瘤发生中也有作用，最近已经证明了这一点。然而，只有少数细胞培养中的体外研究显示 PDAC 细胞中存在 PrPc。我们旨在评估 PDAC 组织中 PrPc 的体内存在情况，作为一种潜在的新生物标志物。
收集并分析了 2018 年 7 月至 2020 年 5 月在我院接受胰腺切除术的 23 名患者的肿瘤样本。比较了 PDAC 组织与对照组织的免疫组织化学和 Western blot。免疫组织化学还用于评估 PrPc 和肿瘤干细胞标志物 CD155 的定位。
所有病例均为中分化 PDAC，23 例中有 19 例（83%）有神经周围侵犯 (PNI)。根据 Western blot 分析，PDAC 组织中 PrPc 的表达明显高于对照组（273.5±44.63 OD 对 100±28.35 OD，p=0.0018）。免疫组织化学证实了这一发现，PDAC 导管中的 PrPc 线性染色更高（127.145±7.56μm 对 75.21±5.01μm，p<0.0001）。PrPc 和 CD155 在导管肿瘤细胞中完全重叠，突出了 PrPc 与癌症干细胞的可能关系。最后，PrPc 的表达与癌症分期有关，与 PNI 有潜在的对应关系。
我们的工作为 PDAC 中 PrPc 水平升高提供了证据。这可能有助于癌症的侵袭性，并提供了一个潜在的新生物标志物。目前正在努力破译其临床意义。
