Abstract 3958: Investigation of HMGB1 as a potential marker for radiation response in muscle invasive bladder cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 3958
• Main Authors: Mansure, Jose J., Shrivastava, Sanhita, Nassim, Roland, Ferbeyre, Gerardo, Kassouf, Wassim
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-3958

Abstract Purpose: Radical cystectomy remains the standard treatment for invasive Bladder Cancer (BC). Radiotherapy is an attractive alternative; however lack of local control of the disease and toxicity associated with it remain problematic. As HMGB1 plays a major role in the cancer associated radio-resistance pathways, our objective is to evaluate its role as a predictive marker for radiation response in BC. Methods: Expression of HMGB1 was characterized in a panel of eight BC cell lines via RT-PCR and Western Blotting. Knockdown of HMGB1 was carried out via shRNA lentiviral system. Correlation of HMGB1 expression and radiation response was done using clonogenic assays in control and shRNA transduced cell lines. Alkaline Comet Assay was used to measure the extent of DNA damage and repair in different cell lines 24hr post 5Gy radiation. Olive Tail moment was used as to quantify the DNA Damage. Results: All cell lines expressed different levels of HMGB1, with BV and UC3 having the lowest and the highest expression of HMGB1 simultaneously. Clonogenic assay results showed that UC3 was resistant to radiation while BV was sensitive. Knockdown of HMGB1 caused the radio-resistant UC3 cells to become highly radio-sensitive, with more than 60% cells dying at 2Gy. Comet assay suggest the involvement of HMGB1 in DNA repair, as a significant DNA damage post radiation was observed in the HMGB1 knockdown cell line. Conclusion: Our results demonstrate that high levels of HMGB1 protein are linked to a more radio-resistant outcome and HMGB1 knockdown leads to an increase in radio-sensitivity. Hence HMGB1 could potentially be used as a radiation response marker in invasive BC. Citation Format: Jose J. Mansure, Sanhita Shrivastava, Roland Nassim, Gerardo Ferbeyre, Wassim Kassouf. Investigation of HMGB1 as a potential marker for radiation response in muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3958. doi:10.1158/1538-7445.AM2014-3958