Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution

Lin, Xiukun; Farooqı, Ammad Ahmad; Qureshi, Muhammad Zahid; Romero, Mirna Azalea; Tabassum, Sobia; Ismail, Muhammad

doi:10.1007/s00005-016-0383-0

Cited by 8 publications

(9 citation statements)

References 41 publications

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“…Several studies have found that the key regulators in maintaining the stemness of ESCs, including Oct4, Sox2, and Nanog, as well as their activation targets are frequently overexpressed in CSCs in many cancers (20)(21)(22). Besides, a set of well-characterized molecules, including CD44, CD133, integrin a2b1, ALDH1A1, and Bmi1, involved in the regulation of CSC self-renewal, metastasis, and drug resistance, has been demonstrated as PCSC markers (23)(24)(25). Using qPCR and immunofluorescence staining, we found that hTERT high prostate cancer cells preferentially expressed these ESC-and PCSC-associated markers ( Fig.…”

Section: Htert High Prostate Cancer Cells Preferentially Express Stemmentioning

confidence: 99%

WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

et al. 2017

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Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERT prostate cancer cells exhibit CSC properties, including a stem cell-associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERT prostate cancer cells, WNT3a dramatically decreased the ratio of hTERT prostate cancer cells undergoing asymmetric division. Increased WNT/β-catenin signal activation was also detected in hTERT prostate cancer cells. hTERT-mediated CSC properties were at least partially dependent on β-catenin. These findings provide novel cellular and molecular mechanisms for the self-renewal of CSC orchestrated by tumor microenvironmental stimuli and intracellular signals. .

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Section: Htert High Prostate Cancer Cells Preferentially Express Stemmentioning

confidence: 99%

WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

et al. 2017

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“…+ phenotype and showed high clonogenic and invasive capacity, while phenotypically basal and genetically unstable [44,45] .…”

Section: Pca Stem Cellsmentioning

confidence: 99%

“…The canonical Wnt signaling pathway plays a critical role in self-renewal and maintenance of stem cells [37] . In PCa, the Wnt signaling pathway has been linked to the progression of androgen-independent disease and bone metastasis [45,48,71] . The inhibition of the Wnt pathway results in the downregulation of CSCs and constitutes an interesting target for treatment [37] .…”

Section: Wnt Signaling Pathwaymentioning

confidence: 99%

Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy

Leão¹,

Domingos

Figueiredo

et al. 2017

Urol Int

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Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies. CSCs are a reservoir of cancer cells that exhibit properties of self-renewal and the ability to reestablish the heterogeneous tumor cell population. The existence of PCa stem cells offers a theoretical explanation for many uncertainties regarding PCa and also for treatment resistance and disease progression once clinical cure is achieved. Therapies targeting CSCs might therefore lead to more effective cancer treatments, divergent from a traditional anti-proliferative approach, based on tumor bulk reduction accompanied by CSC-specific inhibition. Here, we focus on reviewing the historical perspective as well as concepts regarding stem cells and CSCs in PCa. In addition, we will report possible strategies and new clinical approaches that address the CSC-based concept of tumorigenesis in PCa.

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“…In the PC tissues, several cancer stem cell markers, such as CD44 and CD133, were expressed and regulate tumor progression . Active ALDH‐expressing prostate cancer cells are also associated with tumor formation ability .…”

Section: Resultsmentioning

confidence: 99%

“…In the PC tissues, several cancer stem cell markers, such as CD44 and CD133, were expressed and regulate tumor progression. (23) Active ALDH-expressing prostate cancer cells are also associated with tumor formation ability. (24) To clarify the populations of cancer stem cell markers in the organoids and the cells in the urine, we performed flow cytometry (Fig.…”

Section: Resultsmentioning

confidence: 99%

Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells

et al. 2017

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Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell‐derived 3‐D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a human PC organoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell‐derived PC organoids have never been produced. Therefore, we generated PC organoids using the dog urine samples. Urine organoids were successfully generated from each dog with PC. Each organoid showed cystic structures and resembled the epithelial structures of original tissues. Expression of an epithelial cell marker, E‐cadherin, and a myofibloblast marker, α‐SMA, was observed in the urine organoids. The organoids also expressed a basal cell marker, CK5, and a luminal cell marker, CK8. CD49f‐sorted basal cell organoids rapidly grew compared with CD24‐sorted luminal cell organoids. The population of CD44‐positive cells was the highest in both organoids and the original urine cells. Tumors were successfully formed with the injection of the organoids into immunodeficient mice. Treatment with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor, piroxicam, and an mTOR inhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor, GANT61, increased the radiosensitivity in the organoids. These findings revealed that PC organoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment of PC in dogs.

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Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution

Cited by 8 publications

References 41 publications

WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy

Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells

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