Illuminating Cancer Systems with Genetically Engineered Mouse Models and Coupled Luciferase Reporters <i>In Vivo</i>

Kocher, Brandon; Piwnica‐Worms, David

doi:10.1158/2159-8290.cd-12-0503

Cited by 56 publications

(50 citation statements)

References 97 publications

(96 reference statements)

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“…As the sizes of tumors treated with radiation or radiation combined with RK-33 were small, measuring tumor weight or tumor size may not have accurately reflected tumor growth or tumor necrosis. We used luciferase-engineered DU145 cells for bioluminescence imaging on an IVIS system, which is more sensitive and accurate for the early detection of tumor growth and development, tumor cell death, and necrosis (36, 37). The signal we detected, total flux, is proportional to the number of light-emitting cells and the calibrated IVIS system allowed us to monitor tumor growth more accurately and over a long period of time.…”

Section: Resultsmentioning

confidence: 99%

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

et al. 2016

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Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a G1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer.

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Section: Resultsmentioning

confidence: 99%

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

et al. 2016

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“…To study the effect of dietary folate on metastasis, we injected the lateral tail vein of SCID/beige mice with human lung adenocarcinoma A549 cells stably expressing luciferase. This approach allows the monitoring of tumor progression in live animals with the level of luminescence reflecting the tumor burden (39). Two groups of mice were used: one kept on a standard rodent chow (6 ppm folic acid) and another kept on a folate-free chow (0.01 ppm folate).…”

Section: Dietary Folate Promotes Lung Colonization By Cancer Cells Anmentioning

confidence: 99%

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

Oleinik

Helke

Kistner-Griffin

et al. 2014

Journal of Biological Chemistry

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Background: Molecular mechanisms translating effects of folate on metastasis are not clear. Results: Folate restriction inhibits methylation and membrane translocation of Rho GTPases in A549 cancer cells and provides survival advantage in mice with lung cancer. Conclusion: Folate enhances migratory ability and invasiveness of cancer cells through Rho GTPase pathways and promotes metastasis. Significance: This study highlights the interaction between nutrients and metastasis-related signaling.

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“…Tumor progression, however, is a collaboration between the genomic lesions in tumor cells and alterations in the tumor microenvironment [1]. The tumor microenvironment is highly heterogeneous [2] with varying cellular constituents within multiple tumor microdomains such as the leading edge of invasion and perinecrotic or perivascular spaces.…”

Section: Introductionmentioning

confidence: 99%

PDE7B Is a Novel, Prognostically Significant Mediator of Glioblastoma Growth Whose Expression Is Regulated by Endothelial Cells

et al. 2014

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Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM.

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Illuminating Cancer Systems with Genetically Engineered Mouse Models and Coupled Luciferase Reporters In Vivo

Cited by 56 publications

References 97 publications

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

PDE7B Is a Novel, Prognostically Significant Mediator of Glioblastoma Growth Whose Expression Is Regulated by Endothelial Cells

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