Title:
SCALABLE ORGANOTYPIC MODELS OF TUMOR DORMANCY
Document Type and Number:
WIPO Patent Application WO/2014/186782
Kind Code:
A3
Abstract:
Disclosed are synthetic organotypic microvascular niches formed by selfassembly of stromal cells cultured endothelial cells seeded with cells of interest to model and determine dormancy state of these cells of interest in these tissues. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained cancer cell quiescence. Further disclosed are dormancy models, and identified active tumor-promoting, endothelial tip cell-derived factors. This disclosure reveals that stable microvasculature constitutes a 'dormant niche', whereas sprouting neovasculature sparks micrometastatic outgrowth.
Inventors:
GHAJAR CYRUS M (US)
BISSELL MINA J (US)
BISSELL MINA J (US)
Application Number:
PCT/US2014/038514
Publication Date:
March 05, 2015
Filing Date:
May 17, 2014
Export Citation:
Assignee:
UNIV CALIFORNIA (US)
GHAJAR CYRUS M (US)
BISSELL MINA J (US)
GHAJAR CYRUS M (US)
BISSELL MINA J (US)
International Classes:
C12N5/07; A01N1/02; G01N33/53
Foreign References:
| US20060140914A1 | 2006-06-29 | |||
| US20100098739A1 | 2010-04-22 |
Other References:
GHAJAR: "Regulation of Tumor Dormancy by the Perivascular Niche, University of Michigan", BIOMEDICAL ENGINEERING : EVENTS, April 2013 (2013-04-01), Retrieved from the Internet [retrieved on 20140916]
SAUDEMONT ET AL.: "NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells.", BLOOD, vol. 105, no. 6, 2005, pages 2428 - 35, XP002662951, DOI: doi:10.1182/BLOOD-2004-09-3458
KING ET AL.: "Structural and functional characteristics of lung macro- and microvascular endothelial cell phenotypes.", MICROVASC RES., vol. 67, no. 2, 2004, pages 139 - 51
COMHAIR ET AL.: "Human Primary Lung Endothelial Cells in Culture.", AM J RESPIR CELL MOL BIOL., vol. 46, no. 6, 2012, pages 723 - 730
FEHRENBACH ET AL.: "Isolation of murine lung endothelial cells.", AM J PHYSIOL LUNG CELL MOL PHYSIOL., vol. 296, no. 6, 2009, pages L1096 - 103
DURR ET AL.: "Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture.", NAT BIOTECHNOL., vol. 22, no. 8, 2004, pages 985 - 92, XP002354163, DOI: doi:10.1038/nbt993
AGUIRRE-GHISO: "Models, mechanisms and clinical evidence for cancer dormancy", NAT REV CANCER., vol. 7, no. 11, 2007, pages 834 - 46
HETHERIDGE ET AL.: "Uses of the in vitro endothelial-fibroblast organotypic co-culture assay in angiogenesis research.", BIOCHEM SOC TRANS., vol. 39, no. 6, 2011, pages 1597 - 600
PAEZ ET AL.: "Cancer Dormancy: A Model of Early Dissemination and Late Cancer Recurrence.", CLIN CANCER RES., vol. 18, no. 3, 2012, pages 645 - 53
PUTRAL ET AL.: "RNA Interference against Human Papillomavirus Oncogenes in Cervical Cancer Cells Results in Increased Sensitivity to Cisplatin.", MOL PHARMACOL., vol. 68, no. 5, 2005, pages 1311 - 9, XP008118981, DOI: doi:10.1124/MOL.105.014191
"InSphero-media-release-20140424", INSPHERO PUBLISHES 3D TUMOR-STROMA MODEL FOR NON- SMALL CELL LUNG CANCER., 2014, Retrieved from the Internet [retrieved on 20140918]
GHAJAR ET AL.: "The perivascular niche regulates breast tumor dormancy.", NAT CELL BIOL., vol. 15, no. 7, July 2013 (2013-07-01), pages 807 - 17
SAUDEMONT ET AL.: "NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells.", BLOOD, vol. 105, no. 6, 2005, pages 2428 - 35, XP002662951, DOI: doi:10.1182/BLOOD-2004-09-3458
KING ET AL.: "Structural and functional characteristics of lung macro- and microvascular endothelial cell phenotypes.", MICROVASC RES., vol. 67, no. 2, 2004, pages 139 - 51
COMHAIR ET AL.: "Human Primary Lung Endothelial Cells in Culture.", AM J RESPIR CELL MOL BIOL., vol. 46, no. 6, 2012, pages 723 - 730
FEHRENBACH ET AL.: "Isolation of murine lung endothelial cells.", AM J PHYSIOL LUNG CELL MOL PHYSIOL., vol. 296, no. 6, 2009, pages L1096 - 103
DURR ET AL.: "Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture.", NAT BIOTECHNOL., vol. 22, no. 8, 2004, pages 985 - 92, XP002354163, DOI: doi:10.1038/nbt993
AGUIRRE-GHISO: "Models, mechanisms and clinical evidence for cancer dormancy", NAT REV CANCER., vol. 7, no. 11, 2007, pages 834 - 46
HETHERIDGE ET AL.: "Uses of the in vitro endothelial-fibroblast organotypic co-culture assay in angiogenesis research.", BIOCHEM SOC TRANS., vol. 39, no. 6, 2011, pages 1597 - 600
PAEZ ET AL.: "Cancer Dormancy: A Model of Early Dissemination and Late Cancer Recurrence.", CLIN CANCER RES., vol. 18, no. 3, 2012, pages 645 - 53
PUTRAL ET AL.: "RNA Interference against Human Papillomavirus Oncogenes in Cervical Cancer Cells Results in Increased Sensitivity to Cisplatin.", MOL PHARMACOL., vol. 68, no. 5, 2005, pages 1311 - 9, XP008118981, DOI: doi:10.1124/MOL.105.014191
"InSphero-media-release-20140424", INSPHERO PUBLISHES 3D TUMOR-STROMA MODEL FOR NON- SMALL CELL LUNG CANCER., 2014, Retrieved from the Internet
GHAJAR ET AL.: "The perivascular niche regulates breast tumor dormancy.", NAT CELL BIOL., vol. 15, no. 7, July 2013 (2013-07-01), pages 807 - 17
Attorney, Agent or Firm:
WONG, Michelle, Chew (Technology Transfer & Intellectual Property Mgmt. Dept.One Cyclotron Road, MS 56A-012, Berkeley CA, US)
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