Human epithelial basal cells are cells of origin of prostate cancer, independent of CD133 status

Renea A Taylor, Roxanne Toivanen, Mark Frydenberg, John S Pedersen, Laurence Harewood, [Unknown] Australian Prostate Cancer Bio, Anne T Collins, Norman J Maitland, Gail P Risbridger

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on alpha2beta1integrin(hi) expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches; (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17beta-estradiol. Enriched alpha2beta1integrin(hi) basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133(+) stem cells but was consistently observed in the CD133(-) population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133(-) basal cells are more susceptible to tumorigenesis compared to the CD133(+) -enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s).
Original languageEnglish
Pages (from-to)1087 - 1096
Number of pages10
JournalStem Cells
Volume30
Issue number6
DOIs
Publication statusPublished - 2012

Cite this

Taylor, Renea A ; Toivanen, Roxanne ; Frydenberg, Mark ; Pedersen, John S ; Harewood, Laurence ; Australian Prostate Cancer Bio, [Unknown] ; Collins, Anne T ; Maitland, Norman J ; Risbridger, Gail P. / Human epithelial basal cells are cells of origin of prostate cancer, independent of CD133 status. In: Stem Cells. 2012 ; Vol. 30, No. 6. pp. 1087 - 1096.
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title = "Human epithelial basal cells are cells of origin of prostate cancer, independent of CD133 status",
abstract = "Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on alpha2beta1integrin(hi) expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches; (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17beta-estradiol. Enriched alpha2beta1integrin(hi) basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133(+) stem cells but was consistently observed in the CD133(-) population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133(-) basal cells are more susceptible to tumorigenesis compared to the CD133(+) -enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s).",
author = "Taylor, {Renea A} and Roxanne Toivanen and Mark Frydenberg and Pedersen, {John S} and Laurence Harewood and {Australian Prostate Cancer Bio}, [Unknown] and Collins, {Anne T} and Maitland, {Norman J} and Risbridger, {Gail P}",
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Human epithelial basal cells are cells of origin of prostate cancer, independent of CD133 status. / Taylor, Renea A; Toivanen, Roxanne; Frydenberg, Mark; Pedersen, John S; Harewood, Laurence; Australian Prostate Cancer Bio, [Unknown]; Collins, Anne T; Maitland, Norman J; Risbridger, Gail P.

In: Stem Cells, Vol. 30, No. 6, 2012, p. 1087 - 1096.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Taylor, Renea A

AU - Toivanen, Roxanne

AU - Frydenberg, Mark

AU - Pedersen, John S

AU - Harewood, Laurence

AU - Australian Prostate Cancer Bio, [Unknown]

AU - Collins, Anne T

AU - Maitland, Norman J

AU - Risbridger, Gail P

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N2 - Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on alpha2beta1integrin(hi) expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches; (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17beta-estradiol. Enriched alpha2beta1integrin(hi) basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133(+) stem cells but was consistently observed in the CD133(-) population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133(-) basal cells are more susceptible to tumorigenesis compared to the CD133(+) -enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s).

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