Canine transmissible venereal tumour established in immunodeficient mice reprograms the gene expression profiles associated with a favourable tumour microenvironment to enable cancer malignancy

BMC Veterinary Research

Yu-Ling Lin¹  Hirotaka Tomiyasu²  Chen-Si Lin³  Chiao-Hsu Ke³  Wei-Hsiang Huang⁴  Hsiao-Hsuan Huang⁵  Hsin-Chien Chiang⁶ 

[1] Agricultural Biotechnology Research Center, Academia Sinica, 11529, Taipei, Taiwan;Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, 113-8657, Tokyo, Japan;Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1 Sec. 4 Roosevelt Rd., 10617, Taipei, Taiwan;Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, 10617, Taipei, Taiwan;Industrial Development Graduate Program of College of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068, Hsinchu City, Taiwan;Laboratory 2612, Rekiin Biotech Inc., 114737, Taipei, Taiwan;

关键词: Tumour biomarkers;    Infectious cancer;    Canine tumour model;    Immunoediting;    cDNA microarray;   

DOI  :  10.1186/s12917-021-03093-4

来源: Springer

【 摘 要 】

BackgroundCanine transmissible venereal tumours (CTVTs) can cross the major histocompatibility complex barrier to spread among dogs. In addition to the transmissibility within canids, CTVTs are also known as a suitable model for investigating the tumour–host immunity interaction because dogs live with humans and experience the same environmental risk factors for tumourigenesis. Moreover, outbred dogs are more appropriate than inbred mice models for simulating the diversity of human cancer development. This study built a new model of CTVTs, known as MCTVTs, to further probe the shaping effects of immune stress on tumour development. For xenotransplantation, CTVTs were first injected and developed in immunodeficient mice (NOD.CB17-Prkdcscid/NcrCrl), defined as XCTVTs. The XCTVTs harvested from NOD/SCID mice were then inoculated and grown in beagles and named mouse xenotransplantation of CTVTs (MCTVTs).ResultsAfter the inoculation of CTVTs and MCTVTs into immune-competent beagle dogs separately, MCTVTs grew faster and metastasized more frequently than CTVTs did. Gene expression profiles in CTVTs and MCTVTs were analysed by cDNA microarray to reveal that MCTVTs expressed many tumour-promoting genes involved in chronic inflammation, chemotaxis, extracellular space modification, NF-kappa B pathways, and focal adhesion. Furthermore, several well-known tumour-associated biomarkers which could predict tumour progression were overexpressed in MCTVTs.ConclusionsThis study demonstrated that defective host immunity can result in gene instability and enable transcriptome reprogramming within tumour cells. Fast tumour growth in beagle dogs and overexpression of tumour-associated biomarkers were found in a CTVT strain previously established in immunodeficient mice. In addition, dysregulated interaction of chronic inflammation, chemotaxis, and extracellular space modification were revealed to imply the possibly exacerbating mechanisms in the microenvironments of these tumours. In summary, this study offers a potential method to facilitate tumour progression and provide a niche for discovering tumour-associated biomarkers in cancer research.

【 授权许可】

CC BY