Journal article
Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles
Cancer biology & therapy, Vol.8(8), pp.720-729
04/01/2009
DOI: 10.4161/cbt.8.8.7922
PMCID: PMC5498000
PMID: 19242129
Abstract
The vasoactive peptide endothelin-1 (ET-1) has been implicated in promoting the progression of prostate and other cancers though its precise mechanism(s)-of-action remain unclear. To better define the role of ET-1 in prostate cancer progression, we generated prostate cancer cell lines (PC-3 and 22Rv1) that express elevated levels of ET-1. As anticipated, increased ET-1 lead to modest autocrine growth stimulation of PC-3 cells in monolayer culture and increased colony formation in soft agar by both cell lines. Unexpectedly, however, metastatic colonization of 22Rv1 cells expressing elevated levels of ET-1 was reduced, as was the size of subcutaneous tumors produced by both 22Rv1- and PC-3 cells. Based on these data, we hypothesized that high levels of ET-1 may negatively impact the tumor microenvironment. We found that increased ET-1 expression did not consistently inhibit angiogenesis, indicating that this was not the cause of poor tumor growth. As an alternative explanation, we examined whether elevated ET-1 results in local vasoconstriction and thus reduces the blood supply available to the tumor. Consistent with this hypothesis, treatment of mice bearing PC-3 xenografts with a vasodilator increased tumor perfusion and partially restored tumor growth. Moreover, analysis of tumor vascular casts indicated vasoconstriction of tumor-feeding arterioles. Taken together, our data suggest that the local concentration of the ET-1 peptide is critical for determining a balance between its previously unrecognized tumor growth-suppressing activity (vasoconstriction) and known growth-promoting (mitogenesis, survival and angiogenesis) activities. These findings may have implications for the modification of current prostate cancer therapies involving ET-1.
Details
- Title: Subtitle
- Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles
- Creators
- Christine J. Weydert - University of IowaAlison K. Esser - University of IowaRuth A. Mejia - University of IowaJustin M. Drake - University of IowaJ. Matthew Barnes - University of IowaMichael D. Henry - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer biology & therapy, Vol.8(8), pp.720-729
- DOI
- 10.4161/cbt.8.8.7922
- PMID
- 19242129
- PMCID
- PMC5498000
- NLM abbreviation
- Cancer Biol Ther
- ISSN
- 1538-4047
- eISSN
- 1555-8576
- Language
- English
- Date published
- 04/01/2009
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Radiation Oncology; Obstetrics and Gynecology
- Record Identifier
- 9984302191602771
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