Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber)

Abstract

Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research.

Molecular signatures of longevity: Insights from cross-species comparative studies

“…Naked mole rats are also remarkably resistant to cancer, based on multi-year observations of this species’ large colonies (Buffenstein, 2008) and transfection of naked mole rat fibroblasts with activated Ras and SV40 LT to induce oncogenic transformation (Seluanov et al, 2009). Nevertheless, cancer is possible in this species, as recently shown (Delaney et al, 2016; Taylor et al, 2017). Sequencing of the genomes of the naked mole rat (Kim et al, 2011) and a closely related species, the Damaraland mole rat (Fang et al, 2014b), as well as a number of cellular and biochemical studies begin to shed light on the mechanisms for their cancer resistance and long lifespan (Azpurua et al, 2013; Seluanov et al, 2009; Tian et al, 2013).…”

Genome maintenance and bioenergetics of the long-lived hypoxia-tolerant and cancer-resistant blind mole rat, Spalax: a cross-species analysis of brain transcriptome

“…While both rat and Spalax have comparable body weights, their maximum lifespan is ~4 years and ~20 years, respectively7. The naked mole rat ( Heterocephalus glaber) , another hypoxia-tolerant subterranean species of the Bathyergidae family, separated by ~85 million years of evolution from Spalax 1, is also long-lived, and was reported to be less sensitive to spontaneous cancers8, except few cases recently reported9. Molecular adaptations to subterranean life and longevity where suggested for this species, in a brain transcriptome study10.…”

Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

“…Cancer-related mortality can reach up to 90% in mice, which have a maximum lifespan (MLS) of 4 years [22]. In contrast, the similar-sized naked mole rat ( Heterocephalus glaber ), which has an MLS of 32 years, rarely develops cancer [23, 25, 26], furthermore naked mole rat cells are resistant to experimental tumorigenesis [27, 28]. Another long-lived rodent, the blind mole rat ( Spalax sp.…”