Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions

Birnie, Richard; Bryce, Steven D.; Roome, Claire; Dussupt, Vincent; Droop, Alastair P.; Lang, Shona; Berry, Paul A.; Hyde, Catherine; Lewis, John L.; Stower, Michael J.; Maitland, Norman J.; Collins, Anne T.

doi:10.1186/gb-2008-9-5-r83

Cited by 188 publications

(208 citation statements)

References 47 publications

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“…Further break-down of these CT signature genes on the basis of their function, revealed that 13 genes were associated with cell-cell adhesion and six genes were associated with inflammation, suggesting that inflammation and loss of cell-cell adhesion may be early responses of PC cells and may constitute early events associated with CT-mediated metastasis. These results are consistent with proinflammatory phenotype of human PC stem cells, further supporting a possible role of CT-CTR axis in maintaining stemness of PC cells (Untergasser et al 2005, Birnie et al 2008.…”

Section: Discussionsupporting

confidence: 79%

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

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Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer (PC).Although the significance of CT-CTR axis in PC cell growth, invasion, and epithelial to mesenchymal transition has been established, its role in tumor metastasis has not been examined. To examine the role of CT-CTR axis in tumor metastasis, we employed stable CT-CTR activated and silenced system of three PC cell lines, LNCaP cells that lack endogenous CT, PC-3 cells that lack endogenous CTR, and PC-3M cells that co-express CT and CTR. Enforced expression of CT in LNCaP cells and CTR in PC-3 cells increased their ability to form orthotopic tumors and distant metastases in multiple organs. By contrast, silencing of CT expression in PC-3M cells not only reduced their tumorigenicity, but also completely abrogated their metastatic potential. To investigate the effect of in vivo silencing of CT expression on tumor growth, we employed recombinant adeno-associated virus (rAAV) to deliver anti-CT ribozymes in preexisting tumors of nude mice and large probasin promoter (LPB)-Tag transgenic mice. rAAV-CT K treatment not only abrogated the growth of pre-implanted tumors in nude mice, but also significantly reduced the growth of spontaneous tumors in LPB-Tag mice. Analysis of CT upregulated and silenced PC-3M transcriptomes revealed 105 genes affected by the modulation of CT expression. These CT signature genes generated survival, adhesion, pro-inflammatory, and pro-metastatic pathways. Added together, these data indicate a pivotal role for CT-CTR axis in PC metastasis and may serve as a potential therapeutic target for advanced PC.

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Section: Discussionsupporting

confidence: 79%

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

Shah¹,

Thomas²,

Anbalagan³

et al. 2008

Endocrine Related Cancer

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“…Flow cytometry approaches to purifying subsets of epithelial cells based on cell surface marker expression have been combined with xenograft assays to identify putative TICs isolated from mouse prostate cancer models as well as human prostate cancer specimens Kasper 2008 (Collins et al 2005), while molecular analyses of CD133 + a 2 b 1 integrin hi cells revealed a potential cancer stem cell signature that is enriched for components of the JAK-STAT, Wnt, and focal adhesion pathways (Birnie et al 2008). To date, however, the successful use of cell surface markers to isolate cell populations from primary human prostate cancers with tumor-initiating capabilities in grafting assays has not yet been reported.…”

Section: Identification Of Ticsmentioning

confidence: 99%

Molecular genetics of prostate cancer: new prospects for old challenges

Shen¹,

2010

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Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead.

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“…Finding such common traits may help discover the Achilles' heel of CSCs and, subsequently, devise efficient therapeutic www.intechopen.com approaches. There are studies that attempted to characterize the global difference of gene expression in fast-proliferating tumour cells and the corresponding CSCs, and such studies have been useful for confirming the stemness features of the cells (Ivanova et al, 2002;Ramalho-Santoz et al, 2002;Fortunel et al, 2003) or to characterize specific properties of CSCs (Birnie et al, 2008). We have attempted to use microarray analysis to characterize the stemness of several types of cancer cells grown as spheres, including breast and prostate cancer as well as malignant mesotheliomas (Figure 4) (Neuzil et al, unpublished data).…”

Section: Resultsmentioning

confidence: 99%