Translation of triple-negative breast cancer behavior from the xenograft model to human model

• Main Authors: Sanaz Rismanchi, Ahad Muhammadnejad, Elahe Keyhani, Samad Muhammadnejad, Saeid Amanpour
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2016-11-01
• Series: Basic & Clinical Cancer Research
• Subjects: Triple-negative breast cancer; Xenograft models; Angiogenesis; Translational research; Validity
• Online Access: https://bccr.tums.ac.ir/index.php/bccrj/article/view/199
• ISSN: 2228-6527; 2228-5466

Background: For xenograft models of triple-negative breast cancer (TNBC) to be valuable in development of molecularly-targeted drugs, careful characterization is essential to their validation. The present study aimed to validate the TNBC xenograft model with a specific focus on angiogenesis. Methods: Twelve TNBC xenograft tumors and 12 human breast cancer tumors (HTNBC) were included in this study. Both groups were grade III and p53 positive. Nuclear pleomorphism and mitotic count were analyzed by hematoxylin and eosin (H&E) stains respectively. Basal cytokeratin (CK5/6), vimentin, cathepsin-D, Ki-67 (for proliferation), and MVD-CD34 (for angiogenesis) markers were examined by immunohistochemistry (IHC). The association of Microvesseles density (MVD) with Ki-67, nuclear pleomorphism, and mitotic count was assessed in each group separately, and HTNBCs were compared with the xenograft group. Results: The xenograft models showed a significant correlation between angiogenesis (MVD) and cell proliferation (Ki-67), nuclear pleomorphism, and mitotic count (p= 0.0398; p= 0.020; p=0.001, respectively). The HTNBC group also showed a similar trend, except nuclear pleomorphism (p=0.193), which did not correlate with angiogenesis. Comparison between the two groups showed significant changes in cell proliferation (Ki-67 and vimentin). The difference in proliferation rate and vimentin expression between the two groups can be due to biological diversity between human and mice and epithelial-mesenchymal transition (EMT), respectively. Conclusion:  Our results, re-emphasize the significance of angiogenic treatment therapy in patients with TNBC, and further validate the TNBC xenograft model as a valid model for drug discovery and development.