Pathological and genetic aspects of spontaneous mammary gland tumor in Tupaia belangeri (tree shrew)
Pathological and genetic aspects of spontaneous mammary gland tumor in Tupaia belangeri (tree shrew)
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DOI：
10.1371/journal.pone.0233232
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发表时间：
2020-05-18
期刊：
影响因子：
3.7
通讯作者：
Tsukiyama-Kohara, Kyoko
中科院分区：
文献类型：
--
作者：
Hai-Ying, Chi;Tanaka, Yuki;Tsukiyama-Kohara, Kyoko
乳腺癌是全球女性最常见的癌症。这种癌症在日本的发病率正在上升。每年，日本记录的新病例超过7万例，全球约有170万例。许多自发性乳腺肿瘤仍难以完全治愈，需要动物模型来表征其生物学特性、治疗策略和预防措施。目前使用的小鼠模型由于小鼠和人类乳腺之间的结构差异而具有一些局限性。树鼩（Tupaiabelangeri）属于树鼩科（Tupaiidae），与人类乳腺具有较高的遗传同源性和结构相似性。在这里，我们的特点是自发性乳腺肿瘤在61个不同年龄的女性树。本组发生率为24.6%（15/61），同时或异时多发性肿瘤占60%（9/15）。从发病规律看，部分病例可能为家族性乳腺肿瘤，雌树3号、9号和雄树11号的后代发病率较高，为73.3%（11/15）。平均发病年龄2岁3个月，最早10个月。组织化学分析表明，除2例管状乳头状癌（75号和131号）外，其余22例均具有导管内乳头状腺瘤的特征。所有病例均为孕激素受体阳性，91.3%为雌激素受体阳性，4.3%为HER-2阳性。我们还证实了nectin-4在一些乳腺肿瘤细胞中的表达。此外，我们对树鼩进行了细胞学诊断或X线CT。因此，这项研究的结果突出了树作为一个有价值的新的动物模型乳腺肿瘤研究的潜力。
Mammary gland cancer is the most common cancer occurring in women globally. Incidences of this cancer in Japan are on the increase. Annually, more than 70,000 new cases are recorded in Japan and about 1.7 million in the world. Many cases are still difficult to cure completely, and animal models are required for the characterization of the biology, therapeutic strategy, and preventive measures for spontaneous mammary tumor. The mouse model used currently has some limitations owing to structural differences between mouse and human mammary glands. Tupaia belangeri (tree shrew), which belongs to the Tupaiidae family, shows relatively high genetic homology and structural similarity to human mammary glands. Here, we characterized the spontaneous mammary tumors in 61 female tree shrews of different ages. The incidence rate was 24.6% (15/61), and the rate of simultaneous or metachronous multiplex tumors was 60% (9/15). From the incidence pattern, some cases seemed to be of familial mammary gland tumor, as the offspring of female tree shrews No. 3 and 9 and male tree shrew No. 11 showed a high incidence rate, of 73.3% (11/15). Average incidence age for tumor development was 2 years and 3 months, and the earliest was 10 months. Histochemical analysis indicated that spontaneous mammary gland tumors in the tree shrew show the features of intraductal papillary adenomas (22 cases), except 2 tubulopapillary carcinoma cases (No. 75 and 131). All the cases were positive for the progesterone receptor, whereas 91.3% were positive for the estrogen receptor, and 4.3% were HER-2 positive. We have also confirmed the expression of nectin-4 in some mammary tumor cells. Additionally, we subjected tree shrews to cytodiagnosis or X-ray CT. Thus, the findings of this study highlight the potential of the tree shrew as a valuable new animal model for mammary gland tumor study.