Tumor and microenvironment modification during progression of murine orthotopic bladder cancer.
The aim of this study was to monitor changes in the expression of immune-related genes in the bladder after tumor implantation. Mice were orthotopically implanted with MB49-PSA cells (C57BL/6 mice) on day 1 and terminated on days 7, 14, 21, and 28. Another mouse model (MBT-2/C3H mice) was examined at day 7. Gene expression analysis was performed using a TaqMan Low Density Mouse Immune Panel (Applied Biosystems, USA) on RNA extracted from the bladders. Selected genes were reconfirmed by real-time PCR analysis and RT-PCR on the mRNA from other animals. Immune suppressive (IL13, IL1β, PTGS2, NOS2, IL10, CTLA4, and CCL22) and immune stimulatory genes (CSF2, GZMB, IFNγ, CXCL10, TNFα, CD80, IL12a, and IL6) and AGTR2 were increased by day 7. By day 28, IL10, CCL2, CCL5, CXCL11, CTLA4, GZMB, IFNγ, CSF2, and IL6 were significantly increased. Therapeutic strategies involving TH1 induction and TH2 dampening may improve responses to immunotherapy.
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore 119228.
Sin Mun
SM
Tham
Kee Hui
KH
Ng
Sim Hwee
SH
Pook
Kesavan
K
Esuvaranathan
Ratha
R
Mahendran
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen; D058408:Th1-Th2 Balance; D019076:Transgenes; D059016:Tumor Microenvironment / Q000276:immunology; D001743:Urinary Bladder / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D017430:Prostate-Specific Antigen