TITLE:
Molecular Assessment of Non-Muscle Invasive and Muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling
AUTHORS:
Rafael Mamprin Stopiglia, Wagner Eduardo Matheus, Patrick Vianna Garcia, Athanase Billis, Mariana Anteghini Castilho, Vitor Hugo Figueiredo de Jesus, Ubirajara Ferreira, Wagner José Fávaro
KEYWORDS:
Non-Muscle Invasive Bladder Cancer, Muscle Invasive Bladder Cancer, Toll-Like Receptors, Cancer Stem Cell, Stem Cells Biomarkers
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.2,
January
29,
2015
ABSTRACT:
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.