Laboratory of Biology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Veterinary Teaching Hospital, Azabu University, Sagamihara, Japan.
Vet Med Sci. 2021 Mar;7(2):577-585. doi: 10.1002/vms3.397. Epub 2020 Nov 18.
The cell surface glycoprotein CD44 has various types of splicing variants, which contribute to its multiple distinct cellular functions. Recently, it was reported that the CD44v8-10 isoform interacts with the system Xc(-) transporter-related protein (xCT), and inhibits the accumulation of reactive oxygen species by promoting the synthesis of the antioxidant glutathione in human tumour cells. In this study, we investigated the expression and function of CD44 variants and xCT in canine tumours. From semi-quantitative reverse transcription polymerase chain reaction analysis, the mRNA expression of the CD44v8-10 isoform was observed in canine tumour tissues as well as human cases. The overexpression of CD44v8-10 may promote the synthesis of glutathione and enhance the resistance to radiation of canine breast tumour cells. Furthermore, canine xCT mRNA expression was significantly upregulated in the canine breast tumour tissues as compared to the normal tissues surrounding the tumours. To investigate the function of canine xCT, we treated canine tumour cells with the xCT inhibitor sulfasalazine. Consequently, the sulfasalazine-treated cells were more sensitive to oxidative stress than the non-treated cells. Taken together, these results suggested that CD44v8-10 and xCT play important roles in the therapy resistance of canine tumours as well as human tumours.
细胞表面糖蛋白 CD44 具有多种剪接变异体，这些变异体有助于其多种独特的细胞功能。最近有报道称，CD44v8-10 同工型与系统 Xc(-)转运体相关蛋白 (xCT) 相互作用，并通过促进抗氧化谷胱甘肽的合成来抑制人肿瘤细胞中活性氧的积累。在这项研究中，我们研究了犬肿瘤中 CD44 变体和 xCT 的表达和功能。从半定量逆转录聚合酶链反应分析中，观察到 CD44v8-10 同工型的 mRNA 在犬肿瘤组织以及人类病例中表达。CD44v8-10 的过表达可能会促进谷胱甘肽的合成，并增强犬乳腺肿瘤细胞对辐射的抵抗力。此外，与肿瘤周围正常组织相比，犬乳腺肿瘤组织中犬 xCT mRNA 的表达显著上调。为了研究犬 xCT 的功能，我们用 xCT 抑制剂柳氮磺胺吡啶处理犬肿瘤细胞。结果，柳氮磺胺吡啶处理的细胞比未经处理的细胞对氧化应激更敏感。综上所述，这些结果表明 CD44v8-10 和 xCT 在犬肿瘤以及人类肿瘤的治疗耐药性中发挥重要作用。
