Marek Katarzyna, Armando Federico, Asawapattanakul Thanaporn, Nippold Vanessa Maria, Plattet Philippe, Gerold Gisa, Baumgärtner Wolfgang, Puff Christina
Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany.
Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany.
Pathogens. 2023 Jun 27;12(7):877. doi: 10.3390/pathogens12070877.
The immune response plays a key role in the treatment of malignant tumors. One important molecule promoting humoral and cellular immunity is granulocyte-macrophage colony-stimulating factor (GM-CSF). Numerous successful trials have led to the approval of this immune-stimulating molecule for cancer therapy. However, besides immune stimulation, GM-CSF may also accelerate tumor cell proliferation, rendering this molecule a double-edged sword in cancer treatment. Therefore, detailed knowledge about the in vitro function of GM-CSF produced by infected tumor cells is urgently needed prior to investigations in an in vivo model. The aim of the present study was to functionally characterize a persistent infection of canine histiocytic sarcoma cells (DH82 cells) with the canine distemper virus strain Onderstepoort genetically engineered to express canine GM-CSF (CDV-Ond). The investigations aimed (1) to prove the overall functionality of the virally induced production of GM-CSF and (2) to determine the effect of GM-CSF on the proliferation and motility of canine HS cells. Infected cells consistently produced high amounts of active, pH-stable GM-CSF, as demonstrated by increased proliferation of HeLa cells. By contrast, DH82 cells lacked increased proliferation and motility. The significantly increased secretion of GM-CSF by persistently CDV-Ond-infected DH82 cells, the pH stability of this protein, and the lack of detrimental effects on DH82 cells renders this virus strain an interesting candidate for future studies aiming to enhance the oncolytic properties of CDV for the treatment of canine histiocytic sarcomas.
免疫反应在恶性肿瘤治疗中起着关键作用。一种促进体液免疫和细胞免疫的重要分子是粒细胞-巨噬细胞集落刺激因子（GM-CSF）。众多成功的试验促使这种免疫刺激分子被批准用于癌症治疗。然而，除了免疫刺激外，GM-CSF还可能加速肿瘤细胞增殖，这使得该分子在癌症治疗中成为一把双刃剑。因此，在进行体内模型研究之前，迫切需要详细了解受感染肿瘤细胞产生的GM-CSF的体外功能。本研究的目的是对犬瘟热病毒株Onderstepoort进行基因工程改造以表达犬GM-CSF（CDV-Ond），从而对犬组织细胞肉瘤细胞（DH82细胞）的持续感染进行功能特性分析。这些研究旨在：（1）证明病毒诱导产生GM-CSF的整体功能；（2）确定GM-CSF对犬组织细胞肉瘤细胞增殖和运动的影响。如HeLa细胞增殖增加所示，受感染细胞持续产生大量活性、pH稳定的GM-CSF。相比之下，DH82细胞的增殖和运动没有增加。持续被CDV-Ond感染的DH82细胞中GM-CSF分泌显著增加、该蛋白的pH稳定性以及对DH82细胞没有有害影响，使得该病毒株成为未来旨在增强CDV溶瘤特性以治疗犬组织细胞肉瘤研究的一个有趣候选对象。
