Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken.Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments.Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice.Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis.
背景：近几十年来，全球范围内非黑色素瘤皮肤癌的发病率显著上升。为探索鳞状细胞癌的发病机制及潜在治疗方法，已开展多项基于小鼠模型的体内研究。然而，目前尚未对不同无毛小鼠模型（包括有无黑色素类型）以及高胆固醇血症与免疫抑制模型在诱导鳞状细胞癌能力方面进行系统性比较研究。 方法：选取SKH-hr1、SKH-hr2、SKH-hr2+ApoE及免疫缺陷型Nude（Foxn1基因敲除）四种小鼠品系，每周三次接受UVA和UVB照射，初始剂量为1个最小红斑量（MED），每周递增至最大剂量3 MED。监测指标包括临床评估、影像记录、生物物理参数，同时检测蛋白酶体蛋白活性并进行组织病理学评估。 结果：SKH-hr1模型主要发展为光化性角化病，未显著进展为侵袭性鳞状细胞癌（SCC）；而SKH-hr2和SKH-hr2+ApoE模型表现出更高的乳头状瘤和侵袭性SCC形成概率及严重程度，其中后者显示蛋白酶体活性上调。组织病理学分析证实SKH-hr2和SKH-hr2+ApoE模型存在低分化侵袭性SCC，与Nude小鼠中侵袭性较低的SCC及SKH-hr1小鼠中观察到的混合性病变形成对比。 结论：SKH-hr2+ApoE和SKH-hr2小鼠被确定为最适合进一步研究鳞状细胞癌发生的模型，而SKH-hr1小鼠（虽为白化品系）的适用性最低。值得注意的是，蛋白酶体分析揭示了蛋白酶体活性在鳞状细胞癌发生中的潜在作用。
Comparative Study of Cutaneous Squamous Cell Carcinogenesis in Different Hairless Murine Models
肿瘤(癌症)患者之家