Abstract 4955: Role of Angiotensin II in prostate cancer metastasis
Abstract Introduction: At the initial stages prostate cancer development depends on a crucial level of androgenic stimulation but at later stages when it becomes androgen independent the perturbation from androgen receptor axis leads to the development of more aggressive phenotypes with greater meta...
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| Published in: | Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.4955-4955 |
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| Main Authors: | , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
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| Summary: | Abstract
Introduction: At the initial stages prostate cancer development depends on a crucial level of androgenic stimulation but at later stages when it becomes androgen independent the perturbation from androgen receptor axis leads to the development of more aggressive phenotypes with greater metastatic potential. At this stage the growth and progression of prostate cancer is regulated by various local growth factors and neuro-hormones which are altered in prostate cancer microenvironment. Therefore, identifying these factors which are aberrantly expressed in the tumor microenvironment and understanding how these factors are involved in regulating the tumor progression are essential for developing better targeted therapeutic strategy for the treatment of advanced stages of prostate cancer.
Objective: As emerging reports suggest the importance of tissue based renin angiotensin system (RAS) in pathophysiology of the prostate and as studies indicate a lower incidence of cancer and cancer related deaths in patients taking angiotensin receptor blockers (ARBs) (as medication for hypertension), we intend to study the role played by this system in the progression of prostate cancer.
Methods and Results: Our results show that there is limited expression of RAS components, Angiotensin II (AT II), the main bioactive effector peptide of RAS and its receptors, and its receptor Angiotensin receptor type 1( AT1R) and Angiotensin receptor type 2 (AT2R) , in mouse prostate tissues. However, RAS becomes activated in prostate cancer. The expressions of ATII and AT1R are significantly higher in androgen independent orthotopic PC3 prostate tumor tissues. The expression of AT2R remains unaltered during the development of tumor. Therefore to evaluate the role of ATII in prostate cancer progression, in vitro experiments using two androgen independent orthotopic cell lines, PC3 and C4-2 were performed. Both these cell lines express AT1R. Our results indicate that ATII acting through AT1R promotes metastatic behavior such as invasion and migration of prostate cancer cells and inhibition of ATII by blocking AT1R receptor abrogates this action of ATII.
Conclusions: This study identifies a new role of local RAS in the metastatic progression of prostate cancer and will eventually help to develop newer and effective therapeutic strategies in treatment of androgen independent prostate cancer by targeting ATII or AT1R. This strategy can be used either alone or in combination with existi |
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| ISSN: | 0008-5472 1538-7445 |