Prostate cancer (PCa) is the most common non-skin malignancy and the cancer second most responsible for death in men in United States. Prior studies with animal models of PCa and with humans demonstrated that the prostate produces various growth factors. Addition or blocking of these factors alters PCa cell proliferation and other functions. Among these factors, transforming growth factor-?1 (TGF-?) is involved in tumorigenicity, displays potent immunosuppressive activities, and is required for the conversion of conventional CD4+ T cells to FoxP3+ regulatory T (TR) cells. TR cells that express the transcription factor Foxp3 are essential for normal immune function;absence of TR cells results in multi-organ autoimmunity and death. A clear role of TGF-? and its effect on TR during PCa development and progression lacks experimental evidence. In this proposal, we plan to investigate the underlying mechanisms involved in the context of TGF-? and/or TR using PCa cell lines, derived from transgenic mouse for prostate cancer (TRAMP), in C57/B6 mice. Of these cell lines, TRAMP- C1 and TRAMP-C2 form tumors;TRAMP-C3 fails to do so. These mouse cell lines of PCa can be used to obtain the long-term goal of this project, which is to address the fundamental question: Do TR cells and/or TGF-? levels relate to differences in tumorigenicity of the TRAMP cell lines (C1, C2, and C3)? The objective of this project is to define the role of TGF-? production by host cells in response to or TGF-? expression by TRAMP cell lines and to establish the function of TGF-? on the conversion of naive CD4+ T cells into Foxp3-expressing TR cells.

Public Health Relevance

Prostate Cancer is the most common non-skin malignancy and commonly diagnosed cancer, and second most cancer responsible for death in men in United States. To limit the prostate cancer frequency and to expedite the treatment measures, it is important to understand the underlying mechanisms involved during prostate cancer development and progression. Studies in this proposal will help to understand the mechanisms involved during prostate cancer in the context of Transforming Growth Factor- and regulatory T cell-control of anti- tumor immune responses that are essential to the rationale design of tumor vaccines and adoptive immunotherapy of future.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-PCRB-C (O1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Alabama State University
United States
Zip Code
Kumar, Sanjay; Singh, Rajesh; Malik, Shalie et al. (2018) Prostate cancer health disparities: An immuno-biological perspective. Cancer Lett 414:153-165
Singh, Santosh Kumar; Mishra, Manoj K; Eltoum, Isam-Eldin A et al. (2018) CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells. Sci Rep 8:1323
Kumar, Sanjay; Gurshaney, Sanjeev; Adagunodo, Yori et al. (2018) Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer. Front Biosci (Landmark Ed) 23:1987-2000
Kumar, Sanjay; Eroglu, Erdal; Stokes 3rd, James A et al. (2017) Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells. Oncotarget 8:20895-20908
Shamran, Haidar; Singh, Narendra P; Zumbrun, Elizabeth E et al. (2017) Fatty acid amide hydrolase (FAAH) blockade ameliorates experimental colitis by altering microRNA expression and suppressing inflammation. Brain Behav Immun 59:10-20
Shanker, Anil; Thounaojam, Menaka C; Mishra, Manoj K et al. (2017) Innate-Adaptive Immune Crosstalk 2016. J Immunol Res 2017:3503207
Kumar, Sanjay; Stokes III, James A; Dean, Derrick et al. (2017) Biphasic organo-bioceramic fibrous composite as a biomimetic extracellular matrix for bone tissue regeneration. Front Biosci (Elite Ed) 9:192-203
Pozhitkov, Alex E; Neme, Rafik; Domazet-LoŇ°o, Tomislav et al. (2017) Tracing the dynamics of gene transcripts after organismal death. Open Biol 7:
Manne, Upender; Jadhav, Trafina; Putcha, Balananda-Dhurjati Kumar et al. (2016) Molecular Biomarkers of Colorectal Cancer and Cancer Disparities: Current Status and Perspective. Curr Colorectal Cancer Rep 12:332-344
Kumar, Sanjay; Stokes 3rd, James; Singh, Udai P et al. (2016) Targeting Hsp70: A possible therapy for cancer. Cancer Lett 374:156-166

Showing the most recent 10 out of 12 publications