Pathological and genetic aspects of spontaneous mammary gland tumor in Tupaia belangeri (tree shrew)

Abstract

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.

Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche

“…Breast cancer is the most common cancer occurring in women globally. Annually, about 1.7 million new cases are recorded in the world ( Hai-Ying et al, 2020 ). The mammary gland is the milk-producing organ in animals, which continuously develops after birth and fully differentiates upon pregnancy and lactation.…”

The Tree Shrew as a Model for Cancer Research

“…The spontaneous mammary tumors in tree shrews can be histochemically classified into tubulopapillary carcinoma and intraductal papillary adenoma. Of these tumors, 100% are positive for progesterone receptor (PR), 91.3% are positive for estrogen receptor (ER) and 4.3% are positive for human epidermal growth factor receptor 2 (HER-2), according to immunohistochemical analysis ( 70 ). The PTEN/PIK3CA gene is frequently mutated in spontaneous mammary carcinoma in tree shrews, whereas this phenomenon has not been observed in mouse mammary carcinoma models; thus, tree shrews may be a promising animal model for this type of mammary carcinoma ( 71 ).…”

Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview

“…Tree shrews are genetically closer to humans than to rodents [ 5 , 6 ]. The tree shrew has been extensively used as an animal model for biomedical research of different conditions, including myopia [ 7 ], depression [ 8 , 9 ], cancer [ 10 , 11 , 12 ], chemotherapy models [ 13 ], and non-alcoholic fatty liver disease [ 14 ], to name a few. Of note, the tree shrew has also been used for viral infections, and its use in human viral infections is increasing; thus, the tree shrew emerges as a potential small animal model in advancing the knowledge of viral pathogenesis and diseases [ 3 , 15 ].…”