Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature

Klarmann, George J.; Hurt, Elaine M.; Mathews, Lesley; Zhang, Xiaohu; Duhagon, Marı́a Ana; Mistree, Tashan; Thomas, Sabu; Farrar, William L.

doi:10.1007/s10585-009-9242-2

Cited by 190 publications

(187 citation statements)

References 52 publications

(92 reference statements)

Supporting

Mentioning

183

Contrasting

Order By: Relevance

“…Much recent evidence indicates that PCa contains stem/progenitor cells that might play essential roles in prostate tumorigenicity and metastasis; therefore, the therapeutic strategies targeting these cells are emerging (Maitland & Collins 2008, Klarmann et al 2009, Pfeiffer & Schalken 2009, Li & Tang 2011. We speculate that the suppressor role of AR can be applied to the development of new therapies to target self-renewal/ proliferation of stem/progenitor cells and the basal cells as we observed in this study that introducing AR could block selfrenewal/proliferation of these cells.…”

Section: Using Orthotopic Injection Of Ck5supporting

confidence: 59%

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Lee¹,

Tian²,

Huang³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

Early studies have reported the differential roles of androgen receptor (AR) in different types (luminal, basal intermediate, and stromal) of prostate cancer cells. In vivo mouse model tumor studies using the total prostate epithelial knockout mice (pes-ARKO) also revealed that AR played a suppressive role in proliferation of the CK5C luminal epithelial cells. Using three different resources (one human basal epithelial cell line, one mouse basal epithelial originated progenitor cell line, and a basal epithelium-specific ARKO mouse model), we here demonstrated that the AR in basal epithelial cells of normal prostate plays a suppressive role in their proliferation but a positive role in differentiation into luminal epithelial cells. These results led us to conclude that ARs may play a negative role to suppress CK5 C basal epithelial and progenitor cell proliferation, yet play an essential role to drive basal epithelial cells into more differentiated states. These results may explain why differential AR expression in different cell types within normal prostate is needed and suggest that ARs in prostate basal epithelial cells, although expressed at a very low level, are necessary to maintain the balance between progenitor cells and differentiated luminal epithelial cells.

show abstract

Section: Using Orthotopic Injection Of Ck5supporting

confidence: 59%

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Lee¹,

Tian²,

Huang³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. EMT-type cells, which share molecular characteristics with cancer stem cells (CSC), are believed to play critical roles in early cancer metastasis and drug resistance as shown in several human malignancies including prostate cancer (41)(42)(43). We found that LNCaP cells exposed to dihydrotestosterone significantly upregulated the EMT-related protein TWIST1 mRNA levels.…”

Section: Discussionmentioning

confidence: 88%

Indole-3-Carbinol and 3′,3′-Diindolylmethane Modulate Androgen's Effect on C-C Chemokine Ligand 2 and Monocyte Attraction to Prostate Cancer Cells

Kim

Milner

et al. 2013

Cancer Prevention Research

View full text Add to dashboard Cite

Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells and thereby promote recruitment of monocytes. Given the inhibitory effect of broccoli-derived compounds indole-3-carbinol (I3C) and 3,3 0 -diindolylmethane (DIM) on androgen-dependent pathways, we also reasoned that I3C and DIM could modulate the effect of androgen on CCL2-mediated pathways. Dihydrotestosterone was found to induce a time-dependent (0-72 hours) and concentration-dependent (0-1 nmol/L) increase in CCL2 mRNA levels in androgen-responsive human prostate cancer cells (LNCaP). This increase in CCL2 mRNA corresponded with increased secretion of CCL2 protein. The effect of dihydrotestosterone was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction of CCL2. Although dihydrotestosterone also induced TWIST1 mRNA, an epithelialmesenchymal transition-related factor, and purported inducer of CCL2, blocking its expression with small inhibitor RNA did not inhibit dihydrotestosterone induction of CCL2 mRNA. Moreover, conditioned media from androgen-treated cells promoted human monocyte THP-1 cell migration and this effect was blocked by antibody against CCL-2. Both I3C and DIM inhibited promotional effects of dihydrotestosterone on CCL2 and migration. These results show that androgen may regulate CCL2 and promote inflammatory microenvironment in prostate tumors and that this process can be blocked by broccoli-derived compounds.Cancer Prev Res; 6(6); 519-29. Ó2013 AACR.

show abstract

“…Additionally, recent work in our laboratory has shown that invasive prostate cancer cells are more tumorigenic, compared with their non-invasive counterparts [14]. Klarmann et al demonstrated using invasion chambers and highly defined stem cell media that we can enrich for the population that express stem genes and have CSC-like properties in prostate cancer cell lines.…”

Section: Introduction the Concept Of Cancer Stem Cellsmentioning

confidence: 94%

Radioresistance and Cancer Stem Cells: Survival of the Fittest

Sun¹,

Cabarcas

Farrar³

2011

J Carcinog Mutagen

View full text Add to dashboard Cite

Cancer arises from the accumulation of genetic mutations and aberrant epigenetic modifications in normal cells. Cancer stem cells (CSCs) have been described as a unique tumorigenic population of cells within the tumor mass that have the ability to self-renew and differentiate. In the past few years, the existence and nature of CSCs has served as one of the most controversial topics in the field of cancer biology; however, more recently, there is an abundant amount of evidence that demonstrates their existence. CSCs are believed to be responsible for resistance against conventional therapies, such as radiotherapy that contributes to uncontrolled tumor growth, metastasis and subsequently, patient demise. In this review, we summarize the mechanism(s) by which CSCs are radioresistant, including their enhanced DNA damage response, cell cycle status and the role of the CSC niche. Moreover, by using the Oncomine database, we display data from our laboratory and other groups demonstrating that CSCs have an increased expression of radioresistance genes, which are also involved in carcinogenesis, metastasis and patient relapse. In addition, we provide data from prostatospheres derived from primary patient cells demonstrating that the RAN signaling pathway is one of the top upregulated pathways within the CSC population. Therefore, we hypothesize that the RAN signaling pathway is related to the radioresistance property of CSCs. We briefly review this burgeoning field of study on the biological behavior of CSCs and provide new suggestions for the development of future therapies to target radioresistant CSCs in both pharmaceutical investigations and clinical trials.

show abstract

Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature

Cited by 190 publications

References 52 publications

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Indole-3-Carbinol and 3′,3′-Diindolylmethane Modulate Androgen's Effect on C-C Chemokine Ligand 2 and Monocyte Attraction to Prostate Cancer Cells

Radioresistance and Cancer Stem Cells: Survival of the Fittest

Contact Info

Product

Resources

About