Prostate cancer stem cells: A target for new therapies

TY - GEN

T1 - Prostate cancer stem cells: A target for new therapies

AU - Maitland, N. J.

AU - Bryce, S. D.

AU - Stower, M. J.

AU - Collins, A. T.

PY - 2007

Y1 - 2007

N2 - Prostate cancer is now a common disease in men over 50 years of age. Medical therapies for prostate cancer are based on discoveries from the mid-twentieth century, and in the long term are rarely curative. Most treatments are directed towards an androgen receptor-expressing, highly proliferative target cell, which does indeed form the vast majority of cells in a prostate tumour. However, by invoking the existence of a cancer stem cell which, like normal epithelial stem cells in the prostate, does not express androgen receptor and is relatively quiescent, the observed resistance to most medical therapies can be explained. The phenotype of the prostate cancer stem cells is that of a basal cell and cultures derived from cancers, but not benign tissues, express a range of prostate cancer-associated RNAs. Furthermore, stem cells purified on the basis of alpha 2 beta 1 high integrin and CD133 cell surface antigen expression, from an established culture of Gleason 4 (2+2) prostate cancer (P4E6), were able to form multiple intraprostatic tumours in nude mice when grafted orthotopically in a matrigel plug containing human prostatic stroma. The final tumours re-expressed androgen receptor and displayed a histology similar to that of a Gleason 4 cancer.

AB - Prostate cancer is now a common disease in men over 50 years of age. Medical therapies for prostate cancer are based on discoveries from the mid-twentieth century, and in the long term are rarely curative. Most treatments are directed towards an androgen receptor-expressing, highly proliferative target cell, which does indeed form the vast majority of cells in a prostate tumour. However, by invoking the existence of a cancer stem cell which, like normal epithelial stem cells in the prostate, does not express androgen receptor and is relatively quiescent, the observed resistance to most medical therapies can be explained. The phenotype of the prostate cancer stem cells is that of a basal cell and cultures derived from cancers, but not benign tissues, express a range of prostate cancer-associated RNAs. Furthermore, stem cells purified on the basis of alpha 2 beta 1 high integrin and CD133 cell surface antigen expression, from an established culture of Gleason 4 (2+2) prostate cancer (P4E6), were able to form multiple intraprostatic tumours in nude mice when grafted orthotopically in a matrigel plug containing human prostatic stroma. The final tumours re-expressed androgen receptor and displayed a histology similar to that of a Gleason 4 cancer.

KW - ANDROGEN RECEPTOR

KW - HEMATOPOIETIC STEM

KW - EPITHELIAL-CELLS

KW - GENE-EXPRESSION

KW - IDENTIFICATION

KW - CARCINOMA

KW - HETEROGENEITY

KW - PROGRESSION

KW - CARCINOGENESIS

KW - METASTASIS

U2 - 10.1007/2789_2007_050

DO - 10.1007/2789_2007_050

M3 - Conference contribution

SN - 978-3-540-70852-0

SP - 155

EP - 179

BT - Cancer Stem Cells: Novel Concepts and Prospects for Tumor Therapy

A2 - Wiestler, OD

A2 - Haendler, B

A2 - Mumberg, D

PB - Springer

CY - BERLIN

T2 - Cancer Stem Cell Workshop 2004

Y2 - 20 October 2004 through 22 October 2004

ER -