Abstract A16: Characterization of ErbB family expression in intratibial bladder cancer xenografts: Considerations for preclinical modeling

• Published in: Clinical cancer research 2020-08, Vol.26 (15_Supplement), p.A16-A16
• Main Authors: Broses, Luke J., Day, Kathleen C., Udager, Aaron M., Day, Mark L.
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1557-3265.BLADDER19-A16

Background: Approximately 40% of patients with distant metastatic bladder cancer are diagnosed with bone metastases and a dismal 5-year survival rate of less than 10%. The bone has long been thought to act as “soil” for metastatic cells to “seed,” likely due to the favorable, albeit complex microenvironment that comprises various cell types and growth factors. A study by The Cancer Genome Atlas (TCGA) profiling 405 muscle-invasive bladder cancers reported alterations of the receptor tyrosine kinase pathway in 20% of these patients. This included amplification of EGFR in 9% of cases, mutation or amplification of ERBB2 in 9% of cases, and mutation of ERBB3 in 6% of cases. The purpose of this study was to correlate the expression of ErbB family members in human bladder cancer cell lines with their ability to grow as intratibial xenografts in immune-compromised mice. Methods: We performed intratibial injections with six established human bladder cancer cell lines in 22 NSG mice and we allowed these xenografts to grow for five weeks. Four cell lines expressed luciferase and were measured for bioluminescent signals at multiple time points. The resulting formalin-fixed, paraffin-embedded tibiae were processed for immunohistochemistry (IHC) which utilized human specific antibodies to CK8, EGFR, HER2, Ki-67, and uroplakin. Results: The four luciferase-expressing cell lines exhibited increasing bioluminescent signal over the duration of the study (n=14). Five cell lines had positive human anti-Ki-67 staining in the tibia, confirming their growth in the bone after the intratibial injection. All five cell lines maintained expression, and in certain cases overexpression, of EGFR and HER2 in the intratibial xenografts. We observed an 87.5% take rate (n=16) in a subset of bladder cell lines (5 out of 6) and only the UM-UC-12 cell line exhibiting a 0% take rate (n=6). Conclusion: The high take rate of these five cell lines in the tibia exceeded that of previous studies (25-50%), indicating that the take rate is cell line dependent. Characterizing the ErbB expression profile of individual cell lines in the tibia xenograft model is an important consideration before using these xenografts as a preclinical model. Furthermore, ubiquitous expression of ErbB receptors in tibiae xenografts highlights the importance of growth factor signaling in metastatic bladder cancer and the potential for ErbB targeted therapy. Citation Format: Luke J. Broses, Kathleen C. Day, Aaron M. Udager,