Author(s)

Rafael Mamprin Stopiglia¹, Wagner Eduardo Matheus^1*, Patrick Vianna Garcia², Athanase Billis³, Mariana Anteghini Castilho⁴, Vitor Hugo Figueiredo de Jesus⁴, Ubirajara Ferreira¹, Wagner José Fávaro²

¹Department of Urology, School of Medicine, University of Campinas-UNICAMP, Sao Paulo, Brazil.
²Laboratory of Urogenital Carcinogenesis and Immunotherapy, Institute of Biology, University of Campinas-UNICAMP, Sao Paulo, Brazil.
³Department of Pathology, School of Medicine, University of Campinas-UNICAMP, Sao Paulo, Brazil.
⁴Botucatu School of Medicine, Universidade Estadual Paulista-UNESP, Botucatu, Brazil.

Purpose: The main objectives of this study were to characterize and compare the urothelial stem cells (healthy and cancer cells) and TLRs features in the urinary bladder of men without lesionsand with non-muscle-invasive and muscle invasive urothelial tumors. Materials and Methods: Thirty samples of the urinary bladder of 50 to 80-year-old men, with and without diagnosis of malignant urothelial lesions were used. The 30 samples were divided into 3 groups (n = 10 per group): Normal Group; Non-Muscle Invasive Bladder Cancer Group; Muscle Invasive Bladder Cancer Group. The samples were histopathologically and immunohistochemically analyzed. The study was conducted at teaching Hospital of the University of Campinas (UNICAMP). Results: The CD44 and CD133 immunoreactivities were significantly intense in the muscle-invasive cancer group when compared to the other groups. The ABCG2 biomarker demonstrated intense immunoreactivities in both non-muscle and muscle invasive groups, and absent immunoreactivity in the normal group. All groups showed weak CD117 immunoreactivity. Putative Healthy Stem Cells (CD44/CD133/ CD117⁺) occurred in all groups. Putative Cancer Stem Cells (CD44/CD133/ABCG2⁺) only occurred in the non-muscle and muscle invasive cancer groups. TLR2 immunoreactivity was significantly lower in the non-muscle invasive cancer group and absent in the muscle invasive cancer group. TLR4 immunoreactivity was significantly lower in both cancer groups. Conclusions: This study leads us to the conclusion that putative cancer stem cell occurrence was sensitive to the decreased in TLR2 and TLR4 immunoreactivities. Also, TLR2 and TLR4 demonstrated their involvement in the regulation of the different biomarkers for putative healthy and cancer urothelial stem cells, probably acting as negative regulators of urothelial carcinogenesis. Taken together data obtained suggest that use of TLRs agonists could be a promising alternative for the treatment of non-muscle and muscle invasive bladder tumors.

Non-Muscle Invasive Bladder Cancer, Muscle Invasive Bladder Cancer, Toll-Like Receptors, Cancer Stem Cell, Stem Cells Biomarkers

Stopiglia, R. , Matheus, W. , Garcia, P. , Billis, A. , Castilho, M. , de Jesus, V. , Ferreira, U. and Fávaro, W. (2015) Molecular Assessment of Non-Muscle Invasive and Muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling. Journal of Cancer Therapy, 6, 129-140. doi: 10.4236/jct.2015.62014.