scholarly journals Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Steven Fiering ◽  
Lay-Hong Ang ◽  
Judith Lacoste ◽  
Tim D Smith ◽  
Erin Griner ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Cancer Biology ◽  
Xenograft Model ◽  
Open Science ◽  
Original Publication ◽  
Metastasis Formation ◽  
Invasion And Metastasis ◽  
Caveolin 1 ◽  
High Profile ◽  
Subcutaneous Xenograft

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replicating selected results from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012 were selected on the basis of citations and Altimetric scores (<xref ref-type="bibr" rid="bib5a">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ by Goetz and colleagues, published in Cell in 2011 (<xref ref-type="bibr" rid="bib8">Goetz et al., 2011</xref>). The key experiments being replicated are those reported in Figures 7C (a-d), Supplemental Figure S2A, and Supplemental Figure S7C (a-c) (<xref ref-type="bibr" rid="bib8">Goetz et al., 2011</xref>). In these experiments, which are a subset of all the experiments reported in the original publication, Goetz and colleagues show in a subcutaneous xenograft model that stromal caveolin-1 remodels the intratumoral microenvironment, which is correlated with increased metastasis formation. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

scholarly journals Replication Study: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mee Rie Sheen ◽  
Jennifer L Fields ◽  
Brian Northan ◽  
Judith Lacoste ◽  
Lay-Hong Ang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Invasion ◽  
Cancer Biology ◽  
Original Study ◽  
Invasion And Metastasis ◽  
Caveolin 1 ◽  
Primary Mouse ◽  
Metastatic Burden ◽  
The Difference

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Fiering et al., 2015) that described how we intended to replicate selected experiments from the paper ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ (Goetz et al., 2011). Here we report the results. Primary mouse embryonic fibroblasts (pMEFs) expressing caveolin 1 (Cav1WT) demonstrated increased extracellular matrix remodeling in vitro compared to Cav1 deficient (Cav1KO) pMEFs, similar to the original study (Goetz et al., 2011). In vivo, we found higher levels of intratumoral stroma remodeling, determined by fibronectin fiber orientation, in tumors from cancer cells co-injected with Cav1WT pMEFs compared to cancer cells only or cancer cells plus Cav1KO pMEFs, which were in the same direction as the original study (Supplemental Figure S7C; Goetz et al., 2011), but not statistically significant. Primary tumor growth was similar between conditions, like the original study (Supplemental Figure S7Ca; Goetz et al., 2011). We found metastatic burden was similar between Cav1WT and Cav1KO pMEFs, while the original study found increased metastases with Cav1WT (Figure 7C; Goetz et al., 2011); however, the duration of our in vivo experiments (45 days) were much shorter than in the study by Goetz et al. (2011) (75 days). This makes it difficult to interpret the difference between the studies as it is possible that the cells required more time to manifest the difference between treatments observed by Goetz et al. We also found a statistically significant negative correlation of intratumoral remodeling with metastatic burden, while the original study found a statistically significant positive correlation (Figure 7Cd; Goetz et al., 2011), but again there were differences between the studies in terms of the duration of the metastasis studies and the imaging approaches that could have impacted the outcomes. Finally, we report meta-analyses for each result.

scholarly journals Registered report: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Israr Khan ◽  
John Kerwin ◽  
Kate Owen ◽  
Erin Griner ◽  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Biology ◽  
Open Science ◽  
Tumor Cell Proliferation ◽  
Independent Function ◽  
Pten Protein ◽  
Protein Levels ◽  
High Profile ◽  
Tumour Biology

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib9">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘A coding-independent function of gene and pseudogene mRNAs regulates tumour biology’ by <xref ref-type="bibr" rid="bib26">Poliseno et al. (2010)</xref>, published in Nature in 2010. The key experiments to be replicated are reported in Figures 1D, 2F-H, and 4A. In these experiments, Poliseno and colleagues report microRNAs miR-19b and miR-20a transcriptionally suppress both PTEN and PTENP1 in prostate cancer cells (Figure 1D; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). Decreased expression of PTEN and/or PTENP1 resulted in downregulated PTEN protein levels (Figure 2H), downregulation of both mRNAs (Figure 2G), and increased tumor cell proliferation (Figure 2F; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). Furthermore, overexpression of the PTEN 3′ UTR enhanced PTENP1 mRNA abundance limiting tumor cell proliferation, providing additional evidence for the co-regulation of PTEN and PTENP1 (Figure 4A; <xref ref-type="bibr" rid="bib26">Poliseno et al., 2010</xref>). The Reproducibility Project: Cancer Biology is collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published in eLife.

scholarly journals Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Brad Evans ◽  
Erin Griner ◽  
Keyword(s):  
Cancer Cell ◽  
Histone Methylation ◽  
Cancer Biology ◽  
Scientific Research ◽  
Competitive Inhibitor ◽  
Open Science ◽  
High Profile ◽  
Mutant Idh1 ◽  
Mutant Forms

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib3">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases’ by Xu and colleagues, published in Cancer Cell in 2011 (<xref ref-type="bibr" rid="bib15">Xu et al., 2011</xref>). The key experiments being replicated include Supplemental Figure 3I, which demonstrates that transfection with mutant forms of IDH1 increases levels of 2-hydroxyglutarate (2-HG), Figures 3A and 8A, which demonstrate changes in histone methylation after treatment with 2-HG, and Figures 3D and 7B, which show that mutant IDH1 can effect the same changes as treatment with excess 2-HG. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

scholarly journals Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ajay Bhargava ◽  
Madan Anant ◽  
Hildegard Mack ◽  
Keyword(s):  
Tumor Progression ◽  
Cancer Biology ◽  
Kinase Activity ◽  
Scientific Research ◽  
Open Science ◽  
Erk Pathway ◽  
Braf Inhibitors ◽  
Oncogenic Ras ◽  
High Profile

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib4">Errington et al., 2014</xref>). This Registered Report describes the proposed replication plan of key experiments from "Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF" by Heidorn and colleagues, published in Cell in 2010 (<xref ref-type="bibr" rid="bib9">Heidorn et al., 2010</xref>). The experiments to be replicated are those reported in Figures 1A, 1B, 3A, 3B, and 4D. Heidorn and colleagues report that paradoxical activation of the RAF-RAS-MEK-ERK pathway by BRAF inhibitors when applied to BRAFWT cells is a result of BRAF/CRAF heterodimer formation upon inactivation of BRAF kinase activity, and occurs only in the context of active RAS. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

scholarly journals Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis

Cell ◽  
2011 ◽  
Vol 146 (1) ◽  
pp. 148-163 ◽  
Author(s):  
Jacky G. Goetz ◽  
Susana Minguet ◽  
Inmaculada Navarro-Lérida ◽  
Juan José Lazcano ◽  
Rafael Samaniego ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Invasion And Metastasis ◽  
Caveolin 1

scholarly journals Embryonic zebrafish xenograft assay of human cancer metastasis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1682 ◽  
Author(s):  
David Hill ◽  
Lanpeng Chen ◽  
Ewe Snaar-Jagalska ◽  
Bill Chaudhry
Keyword(s):  
Cancer Cells ◽  
Cancer Biology ◽  
Tumour Growth ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Xenograft Model ◽  
Laboratory Model ◽  
Zebrafish Embryos ◽  
Invasion And Metastasis ◽  
Human Cancer Cells

Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells. Furthermore, limits in our ability to accurately monitor early stages of tumour growth and detect micro-metastases likely results in pain and suffering to the mice used for cancer xenograft experiments. Zebrafish (Danio rerio) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.

scholarly journals Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Oliver Fiehn ◽  
Megan Reed Showalter ◽  
Christine E Schaner-Tooley ◽  
Keyword(s):  
Enzyme Activity ◽  
Myeloid Leukemia ◽  
Cancer Biology ◽  
Open Science ◽  
Wild Type ◽  
High Profile ◽  
Isocitrate Dehydrogenase 2 ◽  
The Common ◽  
Idh1 And Idh2 Mutations ◽  
Acute Myeloid

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib3">Errington et al., 2014</xref>). This Registered Report describes the proposed replication plan of key experiments from “The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate” by Ward and colleagues, published in Cancer Cell in 2010 (<xref ref-type="bibr" rid="bib16">Ward et al., 2010</xref>). The experiments that will be replicated are those reported in Figures 2, 3 and 5. Ward and colleagues demonstrate the mutations in isocitrate dehydrogenase 2 (IDH2), commonly found in acute myeloid leukemia (AML), abrogate the enzyme’s wild-type activity and confer to the mutant neomorphic activity that produces the oncometabolite 2-hydroxyglutarate (2-HG) (Figures 2 and 3). They then show that elevated levels of 2-HG are correlated with mutations in IDH1 and IDH2 in AML patient samples (Figure 5). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published by eLife.

scholarly journals Registered report: Interactions between cancer stem cells and their niche govern metastatic colonization

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Francesca Incardona ◽  
M Mehdi Doroudchi ◽  
Nawfal Ismail ◽  
Alberto Carreno ◽  
Erin Griner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Open Science ◽  
Metastatic Niche ◽  
Pulmonary Fibroblasts ◽  
Metastatic Colonization ◽  
High Profile ◽  
Tumor Growth And Metastasis

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Interactions between cancer stem cells and their niche govern metastatic colonization’ by Malanchi and colleagues, published in Nature in 2012 (<xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). The key experiments that will be replicated are those reported in Figures 2H, 3A, 3B, and S13. In these experiments, Malanchi and colleagues analyze messenger RNA levels of periostin (POSTN) in pulmonary fibroblasts, endothelial cells, and immune cells isolated from mice with micrometastases to determine which cell type is producing POSTN in the metastatic niche (Figure 2H; <xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). Additionally, they examine MMTV-PyMT control or POSTN null mice to test the effect of POSTN on primary tumor growth and metastasis (Figures 3A, 3B, and S13; <xref ref-type="bibr" rid="bib10">Malanchi et al., 2012</xref>). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published in eLife.

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