HIF-2α attenuates lymphangiogenesis by up-regulating IGFBP1 in hepatocellular carcinoma

Biology of the Cell
Theresa GeisBernhard Brüne

Abstract

Tumour-associated lymphangiogenesis was identified as an important clinical determinant for the prognosis of hepatocellular carcinoma (HCC) and significantly influences patient survival. However, in this context, little is known about regulation of lymphangiogenesis by hypoxia-inducible factors (HIF). In HCC, mainly HIF-1α was positively correlated with lymphatic invasion and metastasis, whereas a defined role of HIF-2α is missing. We created a stable knockdown (k/d) of HIF-1α and HIF-2α in HepG2 cells and generated co-cultures of HepG2 spheroids with embryonic bodies. This constitutes an in vitro tumour model mimicking the cancer microenvironment and allows addressing the role of distinct HIF isoforms in regulating HCC lymphangiogenesis. In co-cultures with a HIF-2α k/d, lymphangiogenesis was significantly increased, whereas the k/d of HIF-1α showed no effect. The HIF-2α-dependent lymphangiogenic phenotype was confirmed in vivo using matrigel plug assays with supernatants of HIF-2α k/d HepG2 cells. We identified and verified insulin-like growth factor binding protein 1 (IGFBP1) as a HIF-2α target gene. The potential of HepG2 cells to induce lymphangiogenesis in two independent functional assays was significantly enhanced eithe...Continue Reading

References

Mar 1, 1997·Cytokine & Growth Factor Reviews·D R Clemmons
Mar 15, 2001·Current Opinion in Cell Biology·G L Semenza
May 29, 2001·Molecular Pathology : MP·J G ScharfG Ramadori
Oct 16, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Niels ReinmuthLee M Ellis
May 22, 2003·Cardiovascular Research·Agapios SachinidisJürgen Hescheler
Sep 9, 2004·Science's STKE : Signal Transduction Knowledge Environment·Millie Hughes-Fulford
Apr 6, 2005·The Journal of Experimental Medicine·Satoshi HirakawaMichael Detmar
Oct 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Meit BjörndahlYihai Cao
Mar 24, 2006·Breast Cancer Research and Treatment·Sebastian F SchoppmannPeter Birner
May 6, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Donald E Ingber
Sep 8, 2006·Trends in Endocrinology and Metabolism : TEM·Andrew G RenehanAllan Flyvbjerg
Jun 26, 2007·World Journal of Gastroenterology : WJG·Gassimou BangouraSun Jing
Mar 15, 2008·International Journal of Cancer. Journal International Du Cancer·Armin ThelenSven Jonas
Apr 1, 2008·Archives of Medical Research·Ming-Xu DaHong-Wei Tian
May 20, 2008·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Zhen Fan Yang, Ronnie T P Poon
Apr 24, 2009·Current Opinion in Gastroenterology·Beatriz MínguezJosep M Llovet
Apr 24, 2010·Journal of Cellular and Molecular Medicine·Madeleine HannigMaria Wartenberg
Jun 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Heidi MenradBernhard Brüne
Oct 23, 2010·Molecular Cell·Amar J MajmundarM Celeste Simon
Apr 12, 2011·Journal of Surgical Oncology·Tanja HolopainenAnne Saaristo
Jul 7, 2011·Journal of Hematology & Oncology·Jennifer Wu, Andrew X Zhu
Sep 10, 2011·Journal of Cancer Research and Clinical Oncology·Chenfang ZhuYan Gu
Nov 10, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jamie C ZampellBabak J Mehrara
Dec 16, 2011·Nature Reviews. Cancer·Brian KeithM Celeste Simon
Jan 24, 2012·Cancer Cell·Cristina Branco-PriceRandall S Johnson
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Luana SchitoGregg L Semenza
Sep 21, 2013·Journal of Hepatology·Ghassan K Abou-AlfaLeonard B Saltz
Nov 16, 2013·Frontiers of Medicine·Carmen Chak-Lui WongIrene Oi-Lin Ng

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Citations

Jan 25, 2018·Oncogenesis·Varvara PetrovaIvano Amelio
Mar 1, 2017·Molecular Pharmacology·Xin Xin XiongXiao Qian Chen
Aug 29, 2019·Advanced Drug Delivery Reviews·Brianna CoteAdam W G Alani

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