Avian embryo system for PDX and metastasis studies.
Our lab has used for over more than 15 years an optimized system for growing human patient derived and cancer cell line tumors in the avian chick embryo system. This system also allows for engrafting mouse tumors and it can be used to study
tumor cell invasion, intravasation, dissemination and extravasation in lung, liver, brain and bone marrow. Given that the CAM is a 2-3 layer of tissue it is ideal for intra-vital imaging and angiogenesis studies.
The versatility and advantages of the Chick Embryo CAM system were recently used to explore the mechanisms of hypoxia induced dormancy and chemotherapy resistance of disseminated tumor cells: Fluegen G, Avivar-Valderas A, Wang Y, Padgen M,
Williams JK, Nobre AR, Calvo V, Cheun JF, Bravo Cordero J, Entenberg D, Castracane J , Verkhusha V, Keely PJ, Condeelis J and Aguirre-Ghiso, JA. Phenotypic heterogeneity of disseminated tumor cells is preset by primary tumor hypoxic microenvironments.
Nature Cell Biology (2017) doi:10.1038/ncb3465.
Multiple studies from our lab have employed the avian system for modeling metastasis and dormancy. To highlight a few:
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James K. Williams, David Entenberg, Yarong Wang, Alvaro Avivar-Valderas, Michael Padgena, Ashley Clark, Julio A. Aguirre-Ghiso, James Castracane, John S. Condeelis.Validation of a device for the active manipulation of the tumor microenvironment during
intravital imaging. Intravital (2016);5(2). pii: e1182271. PMID: 27790386
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Sosa MS, Parikh F, Maia AG, Estrada Y, Bosch A, Bragado P, Ekpin E, George A, Zheng Y, Lam HM, Morrissey C, Chung CY, Farias EF, Bernstein E, Aguirre-Ghiso JA. NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes. Nat Commun.
2015 Jan 30;6:6170. doi: 10.1038/ncomms7170. PubMed PMID:25636082; PubMed Central PMCID: PMC4313575
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Bragado P., Estrada Y., Parikh F., Krause S., Capobianco C., Farina H.G., Schewe D.M., and Julio A. Aguirre-Ghiso JA. TGFβ2 dictates disseminated tumour cell fate in target organs through TGFβ-RIII and p38α/β signalling.
Nat. Cell.
Bio
.(2013). Nov;15(11):1351-61. doi: 10.1038/ncb2861. Epub 2013 Oct 27. PMID: 24161934.
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Ulrike Begley, Maria Soledad Sosa, Alvaro Avivar-Valderas, Ashish Patil, Lauren Endres, Yeriel Estrada, Clement T.Y. Chan, Dan Su, Peter C. Dedon, Julio A. Aguirre-Ghiso and Thomas Begley. A human tRNA methyltransferase 9-like protein prevents tumor growth
by regulating LIN9 and the hypoxic response. EMBO Mol Med (2013) Feb 4. doi: 10.1002/emmm.201201161
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Paloma Bragado, Yeriel Estrada, Maria Soledad Sosa, Alvaro Avivar-Valderas, David Cannan, Eric Genden, Marita Teng, Aparna C. Ranganathan, Huei-Chi Wen, Avnish Kapoor, Emily Bernstein and Julio A. Aguirre-Ghiso. Analysis of marker-defined HNSCC subpopulations
reveals a dynamic regulation of tumor initiating properties. PLoS One. (2012) ;7(1):e29974. PMCID: PMC3262798
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Alejandro P. Adam, Ajish George, Paloma Bragado, Bibiana V. Iglesias, Denis Schewe, Aparna Ranganathan, Antonis Kourtidis, Douglas S. Conklin and Julio A. Aguirre-Ghiso. Computational identification of a p38SAPK regulated transcription factor network
required for tumor cell quiescence. Cancer Res. (2009) Jul 15;69(14):5664-72. Epub 2009 Jul 7.
- Denis M. Schewe and Julio A. Aguirre-Ghiso. ATF6α-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci U S A. (2008) Jul 29;105(30):10519-24.
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David Liu, Julio A. Aguirre-Ghiso, Yeriel Estrada and Liliana Ossowski. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell (2002); 1: 445-457.
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Julio Aguirre-Ghiso. Inhibition of FAK signaling activated by urokinase receptor induces human carcinoma dormancy in vivo. Oncogene (2002) 21(16): 2513-24.
