Notch suppresses angiogenesis and progression of hepatic metastases

Cancer Research
Debarshi BanerjeeDarrell J Yamashiro

Abstract

The Notch pathway plays multiple key roles in tumorigenesis, and its signaling components have therefore aroused great interest as targets for emerging therapies. Here, we show that inhibition of Notch, using a soluble receptor Notch1 decoy, unexpectedly caused a remarkable increase in liver metastases from neuroblastoma and breast cancer cells. Increased liver metastases were also seen after treatment with the γ-secretase inhibitor PF-03084014. Transgenic mice with heterozygous loss of Notch1 demonstrated a marked increase in hepatic metastases, indicating that Notch1 signaling acts as metastatic suppressor in the liver microenvironment. Inhibition of DLL1/4 with ligand-specific Notch1 decoys increased sprouting of sinusoidal endothelial cells into micrometastases, thereby supporting early metastatic angiogenic growth. Inhibition of tumor-derived JAG1 signaling activated hepatic stellate cells, increasing their recruitment to vasculature of micrometastases, thereby supporting progression to macrometastases. These results demonstrate that inhibition of Notch causes pathologic activation of liver stromal cells, promoting angiogenesis and growth of hepatic metastases. Our findings have potentially serious implications for Notch i...Continue Reading

References

Jul 1, 1984·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y YokoiK Usui
Mar 15, 1994·Genes & Development·P J SwiatekT Gridley
Jan 19, 2002·Differentiation; Research in Biological Diversity·C MailhosD Ish-Horowicz
Feb 26, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elvira OlasoFernando Vidal-Vanaclocha
Sep 2, 2005·British Journal of Cancer·O HopferS Aebi
Dec 22, 2006·Nature·Irene Noguera-TroiseGavin Thurston
Mar 25, 2009·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Fernando Vidal-Vanaclocha
Sep 3, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Iris SawitzaDieter Häussinger
Feb 12, 2010·Nature·Minhong YanGreg D Plowman
Jan 27, 2011·The Journal of Clinical Investigation·Zhenyi LiuRaphael Kopan
Aug 10, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maryam FouladiRichard J Gilbertson
Apr 25, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anthony W TolcherJennifer J Wheler
May 2, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ian KropPatricia Lorusso
Jan 8, 2013·Pflügers Archiv : European journal of physiology·Claus Hellerbrand
Sep 27, 2013·Vascular Cell·Sonia L HernandezDarrell J Yamashiro
Oct 1, 2013·Pharmacology & Therapeutics·Naoko TakebeSherry X Yang
Sep 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wells A MessersmithPatricia M LoRusso

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Citations

Jun 23, 2015·Immunology Letters·Maria Teresa P de AquinoAnil Shanker
Apr 6, 2016·Journal of Medicinal Chemistry·Rajesh KumarDela Golshayan
Jun 7, 2016·Critical Reviews in Oncology/hematology·Jing LiuGuo-Jun Zhang
Jul 19, 2019·Biological Chemistry·Dieter Häussinger, Claus Kordes
Sep 25, 2015·Aging·Debarshi BanerjeeDarrell J Yamashiro
Feb 22, 2017·The Journal of Clinical Investigation·Cyrill GéraudSergij Goerdt
Oct 28, 2017·Chemical Biology & Drug Design·Peter DobranowskiPeter C Black
Apr 6, 2018·International Journal of Molecular Medicine·Eva SkarmoutsouClaudio Guarneri
Oct 17, 2018·Angiogenesis·Sonia L HernandezJessica J Kandel
Dec 3, 2020·Genes & Development·Minhong Shen, Yibin Kang
Nov 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pnina Brodt
Feb 7, 2021·International Journal of Molecular Sciences·Gemma Garcia-ViciénDavid G Molleví
Mar 22, 2021·Angiogenesis·Philipp-Sebastian KochHellmut G Augustin
May 1, 2021·Cancers·Colin H QuinnElizabeth A Beierle

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