Documents in the NTIS Technical Reports collection are the results of federally funded research. They are directly submitted to or collected by NTIS from Federal agencies for permanent accessibility to industry, academia and the public.  Before purchasing from NTIS, you may want to check for free access from (1) the issuing organization's website; (2) the U.S. Government Printing Office's Federal Digital System website http://www.gpo.gov/fdsys; (3) the federal government Internet portal USA.gov; or (4) a web search conducted using a commercial search engine such as http://www.google.com.
Accession Number ADA564157
Title Role of IKKalpha and STAT3 in the Emergence of Castration-Resistant Prostate Cancer.
Publication Date Jun 2012
Media Count 21p
Personal Author M. Ammirante
Abstract Recent data strongly suggest that inflammation plays a key role in emergence of tumors and metastases. I previously found that androgen ablation causes infiltration of regressing prostate tumors with immune cells, including B cells, that produce lymphotoxin, which activates IKKalpha and STAT3, in prostate tumor cells that have survived hormone withdrawal, thereby accelerating the emergence of castration-resistant prostate cancer. These results suggest that the inflammatory response associated with death of the primary tumor is an important driver of castration-resistant and metastatic disease. I found that myofibroblasts activated in an autocrine way by castration-induced hypoxia, express CXCL13, which is responsible for the recruitment of B cells in the tumor remnants. Depletion of myofobroblasts results in a delay of the emergence of the castration resistant prostate cancer and in a significant reduction of the number of B cells infiltrating the tumors. I also found that a specific TGF-beta inhibitor can inhibit the activation of myofibroblasts after castration and produced a delay in the emergence of the castration resistant prostate cancer as well. These findings suggest that myofibroblasts and TGF-beta signaling are required for the recruitment of B cells in the tumor remnants and for the emergence of castration resistant prostate cancer.
Keywords Activation
B lymphocytes
Castration resistant prostate cancer
Cells(Biology)
Diseases
Drug withdrawal
Excision
Hormones
Hypoxia
Ikkalpha activation
Immunity
Inflammation
Inhibitors
Metastasis
Myofibroblasts
Neoplasms
Prostate cancer
Prostate gland
Resistance(Biology)
Response(Biology)
Stat3 activation
Testes
Tgf-beta inhibitor

 
Source Agency Non Paid ADAS
NTIS Subject Category 57E - Clinical Medicine
Corporate Author California Univ., San Diego, La Jolla.
Document Type Technical report
Title Note Annual summary rept. 1 Jun 2011-31 May 2012.
NTIS Issue Number 1302
Contract Number W81XWH-11-1-0426

Science and Technology Highlights

See a sampling of the latest scientific, technical and engineering information from NTIS in the NTIS Technical Reports Newsletter

Acrobat Reader Mobile    Acrobat Reader