Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Nov 10;3(2):128-38.

Androgen deprivation and stem cell markers in prostate cancers

Yao Tang  1 , Anne W Hamburger, Linbo Wang, Mohammad Afnan Khan, Arif Hussain
Affiliations

Androgen deprivation and stem cell markers in prostate cancers

Yao Tang et al. Int J Clin Exp Pathol. .

Abstract

In our previous studies using human LNCaP xenografts and TRAMP (transgenic adenocarcinoma of mouse prostate) mice, androgen deprivation therapy (ADT) resulted in a temporary cessation of prostate cancer (PCa) growth, but then tumors grew faster with more malignant behaviour. To understand whether cancer stem cells might play a role in PCa progression in these animal models, we investigated the expressions of stem cell-related markers in tumors at different time points after ADT. In both animal models, enhanced expressions of stem cell markers were observed in tumors of castrated mice, as compared to non-castrated controls. This increased cell population that expressed stem cell markers is designated as stem-like cells (SLC) in this article. We also observed that the SLC peaked at relatively early time points after ADT, before tumors resumed their growth. These results suggest that the SLC population may play a role in tumor re-growth and disease progression, and that targeting the SLC at their peak-expression time point may prevent tumor recurrence following ADT.

Keywords: Prostate cancer; TRAMP mice; androgen deprivation; stem-like cells; xenograft tumor.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Response of LNCaP tumors to castration. A. Tumor volumes at different time points (5 mice for control and 10 mice for castrated groups at each time point). Mean tumor volume at each time point was normalized to the initial volume at day-0 (castration day). B. Ki67+ cells at different time points post castration. Three mice were evaluated per time point for both control and castration groups. Images (5-10/sample) were digitized using MCID7.0 software. A sharp increase in the number of proliferating cells was observed between day-15 and day-20 in castrated mice.
Figure 2
Figure 2
Expression of CD44 and c-Kit in LNCaP xenografts after castration. A. IHC. Cryosections of tumors from day-15 (n=5) and day-30 (n=5) time points were reacted individually with CD44 (200×) and c-Kit (100×) antibodies. Inserts represent negative controls. Images were digitized using MCID7.0 software and data analyzed with student t-test (right panel). B. Real-time PCR. CD44 gene expression in tumors at day-15 (n=3) and day-30 (n=3) relative to controls (n=3).
Figure 3
Figure 3
Stem cell related proteins in LNCaP xenografts after castration. A. Representative western blots of stem cell-related proteins in tumors at day-15 and day-30 after castration and in non-castrated controls. 30 μg of protein extracts were loaded per lane. B. Densitometry evaluation of western blot results. Bars represent results of 3 experiments ±S.D.
Figure 4
Figure 4
Comparison of TRAMP prostates at 4 wks and 12 wks of age. A. Representation of the impact of time at castration on tumor development in TRAMP mice. B. Upper panel. Histopathology (H&E stain; 100×) shows neoplastic proliferation in the prostate glands of 12-wk-old non-castrated mice (n=7) but not in noncastrated 4-wk-old mice (n=4). Lower panel. Immunostaining for Sca-1 (200×) shows that only tumor cells are Sca-1+ in 12-wk-old prostates, while Sca-1 is not detected in 4-wk-old prostates. Insert box is negative control.
Figure 5
Figure 5
Expression of stem cell markers in TRAMP mice after castration.A.IHC. Representative prostates from mice 10 wks (Cas-10; n=5) and 20 wks (Cas-20; n=5) post castration immunostained for Sca-1, CD133, and c-Kit (100×). Insert boxes are negative controls.B. Western blots. 30 μg of protein extracts from prostate DLP lobes of Cas-10 (n=5) and Cas-20 mice (n=5) were analyzed for bcl-2 and Grp78 expression.C. The proportion of Sca-1+ cells in wild-type (wk 12; n=2), Cas-10 (n=2) and Cas-20 (n=2) mouse prostates. Sca-1+ cells were isolated with anti-Sca-1 antibody conjugated magnetic beads. The proportion of Sca-1+ cells was determined relative to the total number of single cells in suspension.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11. - PubMed
    1. Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells–perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–44. - PubMed
    1. Fabian A, Barok M, Vereb G, Szollosi J. Die hard: Are cancer stem cells the bruce willises of tumor biology? Cytometry A. 2009;75(1):67–74. - PubMed
    1. Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100(9):672–9. - PubMed
    1. Dylla SJ, Beviglia L, Park IK, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3(6):e2428. - PMC - PubMed

Publication types

LinkOut - more resources