Proliferative Heterogeneity in the Human Prostate: Evidence for Epithelial Stem Cells

Hudson, David L.; O’Hare, Michael J.; Watt, Fiona M.; Masters, J. R. W.

doi:10.1038/labinvest.3780132

Cited by 151 publications

(123 citation statements)

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“…GST-p), all localize preferentially in the basal cell compartment. That the adult human prostate contains stem cells (SCs) is also supported by the observation that a small number of cells within the prostate possess tremendous proliferative capacity and can form glandular-like structures in reconstituted systems (Hudson et al, 2000). Several populations of putative human prostate stem/progenitor cells have been reported, which include CK5 and CK18 double-positive (CK5 þ /CK18 þ ) intermediate cells (van Leenders et al, 2000;Wang et al, 2001;Tran et al, 2002;Garraway et al, 2003;Bhatia et al, 2005), the side population (SP) cells (Bhatt et al, 2003), and small populations of cells that preferentially express cell surface molecules CD44 (Liu et al, 1997), a2b1 (Collins et al, 2001), or CD133 (Richardson et al, 2004).…”

Section: Introductionmentioning

confidence: 94%

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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Section: Introductionmentioning

confidence: 94%

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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“…This is partially based on the preferential survival of basal cells after castration and their ability to repopulate the luminal compartment upon androgen add-back (Isaacs 1987;Bonkhoff and Remberger 1996). In vitro studies have also shown that PSCA -basal cells can give rise to PSCA + intermediate cells coexpressing basal and luminal cytokeratins (Tran et al 2002) that can differentiate into luminal cells (Hudson et al 2000;Xin et al 2007). Other investigators have proposed a branched model of differentiation where the luminal and basal cells are in separate lineages, maintained by separate progenitor cells (Fig.…”

Section: The Prostate Gland and Adult Prostate Stem Cellsmentioning

confidence: 99%

“…2A), further indicating that this assay promotes differentiation. Hudson et al (2000) reported that two types of colonies can grow from primary human prostate cells: type I intermediate colonies and rare type II primitive basal cell colonies, suggesting that both stem and progenitor cells can thrive in this culture. These findings demonstrate that this assay could be Immunofluorescence stains show that colonies coexpress the luminal (CK8) and basal (CK5) cytokeratins (middle).…”

Section: In Vitro Colony-forming Unit Assaymentioning

confidence: 99%

“…Mammary and neural tissues can be cultured on solid substrate where they undergo differentiation in a hormone-, growth-factor-, or cell-cell interaction-regulated process (Reynolds and Weiss 1996;Dontu et al 2003). Some of these methods were combined to develop in vitro prostate colony-forming unit (cfu) assays, in which dissociated adult prostate epithelial cells form colonies on top of feeder cells (Hudson et al 2000;Uzgare et al 2004;Lawson et al 2007).…”

Section: In Vitro Colony-forming Unit Assaymentioning

confidence: 99%

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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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“…It is lagging behind most other cell types as usual. Evidence has been published for normal prostate epithelial stem or progenitor cells in the human [18][19][20] and mouse prostate. [21][22][23][24][25] Mouse data suggest that the stem cell compartment lies towards the base of the ducts near where they join the urethra.…”

mentioning

confidence: 99%