Analysis and sorting of prostate cancer cell types by flow cytometry

Liu, Alvin Y.; True, Lawrence D.; LaTray, Leah; Ellis, William; Vessella, Robert L.; Lange, Paul H.; Higano, Celestia S.; Hood, Leroy; Engh, Ger van den

doi:10.1002/(sici)1097-0045(19990801)40:3<192::aid-pros7>3.0.co;2-f

Cited by 44 publications

(25 citation statements)

References 18 publications

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“…Most prostate cancers are adenocarcinomas that express markers associated with luminal epithelial cells such as CK8, AR, and prostate-specific antigen (PSA). Cells that express only basal markers such as CK5, CK14, and p63 are rarely observed in human cancers, leading to speculations that prostate cancer must initiate in a luminal progenitor or mature luminal cell that reacquired self-renewal (Nagle et al 1987;Liu et al 1999). Differentiated cells significantly outnumber primitive cells in all tissues.…”

Section: The Cell Of Origin For Prostate Cancermentioning

confidence: 99%

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Lukacs¹,

Lawson²,

Long-zuo³

et al. 2008

Cold Spring Harbor Symposia on Quantitative Biology

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Prostate cancer is a leading cause of cancer-related death in adult men. It can regress dramatically upon antihormonal therapy, but it often recurs in a more aggressive, androgen-independent form. Defining the prostate tissue stem cells (PrSCs) and their involvement in cancer initiation and maintenance may lead to better therapeutics. Using a tissue-regeneration model in which dissociated prostate epithelial cells mixed with inductive mesenchyme give rise to prostatic tubules, we have identified a small population of prostate cells that contains multiple stem cell characteristics. In this system, prostate cancer can be initiated by autocrine or paracrine growth factor signaling and intracellular overexpression of genes often found mutated in human prostate cancer. Using an in vitro prostate sphere assay, we further defined the PrSC population and demonstrated their selfrenewal and multilineage differentiation capabilities. Microarray analyses of the stem-and non-stem-cell populations have assisted us in finding and evaluating additional markers that can better define the PrSC population and further delineate the different cell types of the prostate, including those that serve as the target cell for tumor initiation.

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Section: The Cell Of Origin For Prostate Cancermentioning

confidence: 99%

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Lukacs¹,

Lawson²,

Long-zuo³

et al. 2008

Cold Spring Harbor Symposia on Quantitative Biology

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“…It would therefore be advantageous to target cancer stem cells. It is not known, however, if cancer stem cells resemble normal stem cells, 2 TA cells 21,23 or dedifferentiated luminal cells 24,25 and, as with BPH, we need definitive stem-cell markers to address this question.…”

Section: Stem Cells and Prostate Diseasementioning

confidence: 99%

Epithelial stem cells in human prostate growth and disease

Hudson

2004

Prostate Cancer Prostatic Dis

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“…Furthermore, although CD44 expression is reported to be reduced in metastases (Nagabhushan et al, 1996;De Marzo et al, 1998;Noordzij et al, 1999), the CD44 þ PCa cells are found to predominate in two visceral metastases (Liu et al, 1999). Similar to expression studies, the potential role of CD44 in PCa development and metastases is controversial -although some studies show a tumor-suppressive function of CD44 in overexpression experiments (Gao et al, 1997(Gao et al, , 1998, many other studies implicate CD44 in PCa cell proliferation, adhesion, migration, and invasion in vitro as well as in metastatic dissemination in vivo (Lokeshwar et al, 1995;Paradis et al, 1998;Liu et al, 1999;Draffin et al, 2004;Omara-Opyene et al, 2004). Many studies mentioned above utilize either human tissues to carry out correlative immunohistochemistry (IHC) or bulk-cultured PCa cells to carry out overexpression experiments and the key experiment of using purified CD44 þ and CD44 À cells from the same culture or tumor to compare their potentially different biological and tumorigenic properties has not yet been done.…”

Section: Introductionmentioning

confidence: 97%

“…The relationship between CD44 expression and tumor grade is also uncertain -one study shows a strong correlation between Gleason grade of the tumor and loss of CD44 expression (De Marzo et al, 1998), whereas another reports no correlation (Paradis et al, 1998). Furthermore, although CD44 expression is reported to be reduced in metastases (Nagabhushan et al, 1996;De Marzo et al, 1998;Noordzij et al, 1999), the CD44 þ PCa cells are found to predominate in two visceral metastases (Liu et al, 1999). Similar to expression studies, the potential role of CD44 in PCa development and metastases is controversial -although some studies show a tumor-suppressive function of CD44 in overexpression experiments (Gao et al, 1997(Gao et al, , 1998, many other studies implicate CD44 in PCa cell proliferation, adhesion, migration, and invasion in vitro as well as in metastatic dissemination in vivo (Lokeshwar et al, 1995;Paradis et al, 1998;Liu et al, 1999;Draffin et al, 2004;Omara-Opyene et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells

et al. 2006

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CD44 is a multifunctional protein involved in cell adhesion and signaling. The role of CD44 in prostate cancer (PCa) development and progression is controversial with studies showing both tumor-promoting and tumor-inhibiting effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues to carry out correlative or overexpression experiments. The key experiment using prospectively purified cells has not been carried out. Here we use FACS to obtain homogeneous CD44 þ and CD44 À tumor cell populations from multiple PCa cell cultures as well as four xenograft tumors to compare their in vitro and in vivo tumor-associated properties. Our results reveal that the CD44 þ PCa cells are more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic CD44 À PCa cells. Subsequent molecular studies demonstrate that the CD44 þ PCa cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse-chase experiments reveal that CD44 þ cells colocalize with a population of intermediate label-retaining cells. Second, CD44 þ PCa cells express higher mRNA levels of several 'stemness' genes including Oct-3/4, Bmi, b-catenin, and SMO. Third, CD44 þ PCa cells can generate CD44 À cells in vitro and in vivo. Fourth, CD44 þ PCa cells, which are AR À , can differentiate into AR þ tumor cells. Finally, a very small percentage of CD44 þ PCa cells appear to undergo asymmetric cell division in clonal analyses. Altogether, our results suggest that the CD44 þ PCa cell population is enriched in tumorigenic and metastatic progenitor cells.

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Analysis and sorting of prostate cancer cell types by flow cytometry

Cited by 44 publications

References 18 publications

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Epithelial stem cells in human prostate growth and disease

Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells

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