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
Drug withdrawal
Ikkalpha activation
Prostate cancer
Prostate gland
Stat3 activation
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

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