Developmental signaling pathways in brain tumor‐derived stem‐like cells

Clark, Paul A.; Treisman, Daniel M.; Ebben, Johnathan; Kuo, John S.

doi:10.1002/dvdy.21381

Cited by 60 publications

(57 citation statements)

References 164 publications

(196 reference statements)

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“…The cluster analysis indicates the expression intensity (see adjoining legends), gene name, and GenBank accession number. Endocrine-Related Cancer (2008) 15 953-964 www.endocrinology-journals.org Notch and Hedgehog, and tumor suppressor genes such as phosphatase and tensin homolog on chromosome 10 and tumor protein p53, are believed to be deregulated in cancer stem cells, leading to uncontrolled self-renewal and generation of tumors that are resistant to conventional therapies (He & Jablons 2006, Ailles & Weissman 2007, Clark et al 2007, Dreesen & Brivanlou 2007, Grinstein & Wernet 2007, Katoh & Katoh 2007, Campbell et al 2008, Eyler & Rich 2008, Lee & Vasioukhin 2008. Considering that the modulation of CT-CTR axis in three different PC cell lines remarkably altered their metastatic potential raises a critical question: does active CT-CTR autocrine axis increases the stemness of PC cells?…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Upregulation of the Notch signalling pathway is a causative agent in T-cell leukemia and perhaps other cancers (Clark et al, 2007;Farnie and Clarke, 2007;Roy et al, 2007) (Hawkins and Russell, 2008). In Drosophila neuroblasts of the SOPs, Lgl is important in the asymmetric distribution of Numb (Betschinger et al, 2003;Wirtz-Peitz et al, 2008), an inhibitor of Notch signalling.…”

Section: Scribble/dlg/lgl and Other Polarity Complexesmentioning

confidence: 99%

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

et al. 2008

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The neoplastic tumour suppressors, Scribble, Dlg and Lgl, originally discovered in the vinegar fly Drosophila melanogaster, are currently being actively studied for their potential role in mammalian tumourigenesis. In Drosophila, these tumour suppressors function in a common genetic pathway to regulate apicobasal cell polarity and also play important roles in the control of cell proliferation, survival, differentiation and in cell migration/invasion. The precise mechanism by which Scribble, Dlg and Lgl function is not clear; however, they have been implicated in the regulation of signalling pathways, vesicle trafficking and in the Myosin II-actin cytoskeleton. We review the evidence for the involvement of Scribble, Dlg, and Lgl in cancer, and how the various functions ascribed to these tumour suppressors in Drosophila and mammalian systems may impact on the process of tumourigenesis.

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“…BTSCs enriched in this manner demonstrate stem cell-like properties, such as expression of stem cell markers (CD133, nestin), differentiation to multiple neural lineages (glial and neuronal), and tumor initiation in an orthotopic immunodeficient mouse model with as few as 100 cells 18 . Although some debate exists about purification and maintenance of BTSCs 1,[19][20][21] , sphere-grown BTSCs better maintain the phenotype and genotype of the parental tumor [22][23][24] .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

Huang

Agrawal

Clark

et al. 2011

JoVE

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In the last 40 years, the United States invested over 200 billion dollars on cancer research, resulting in only a 5% decrease in death rate. A major obstacle for improving patient outcomes is the poor understanding of mechanisms underlying cellular migration associated with aggressive cancer cell invasion, metastasis and therapeutic resistance 1 . Glioblastoma Multiforme (GBM), the most prevalent primary malignant adult brain tumor 2 , exemplifies this difficulty. Despite standard surgery, radiation and chemotherapies, patient median survival is only fifteen months, due to aggressive GBM infiltration into adjacent brain and rapid cancer recurrence 2 . The interactions of aberrant cell migratory mechanisms and the tumor microenvironment likely differentiate cancer from normal cells 3 . Therefore, improving therapeutic approaches for GBM require a better understanding of cancer cell migration mechanisms. Recent work suggests that a small subpopulation of cells within GBM, the brain tumor stem cell (BTSC), may be responsible for therapeutic resistance and recurrence. Mechanisms underlying BTSC migratory capacity are only starting to be characterized 1,4 . Due to a limitation in visual inspection and geometrical manipulation, conventional migration assays 5 are restricted to quantifying overall cell populations. In contrast, microfluidic devices permit single cell analysis because of compatibility with modern microscopy and control over microenvironment [6][7][8][9] .We present a method for detailed characterization of BTSC migration using compartmentalizing microfluidic devices. These PDMS-made devices cast the tissue culture environment into three connected compartments: seeding chamber, receiving chamber and bridging microchannels. We tailored the device such that both chambers hold sufficient media to support viable BTSC for 4-5 days without media exchange. Highly mobile BTSCs initially introduced into the seeding chamber are isolated after migration though bridging microchannels to the parallel receiving chamber. This migration simulates cancer cellular spread through the interstitial spaces of the brain. The phase live images of cell morphology during migration are recorded over several days. Highly migratory BTSC can therefore be isolated, recultured, and analyzed further.

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Developmental signaling pathways in brain tumor‐derived stem‐like cells

Cited by 60 publications

References 164 publications

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

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

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

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