Overexpression of Receptor Tyrosine Kinase EphB4 Triggers Tumor Growth and Hypoxia in A375 Melanoma Xenografts: Insights from Multitracer Small Animal Imaging Experiments

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Christin NeuberJens Pietzsch

Abstract

Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron emission tomography. Vascularization was investigated by fluorescence imaging in vivo and ex vivo. The approach was completed by magnetic resonance imaging, radioluminography ex vivo, and immunohistochemical staining for blood and lymph vessel markers. Results revealed EphB4 to be a positive regulator of A375 melanoma growth, but a negative regulator of tumor vascularization. Resulting in increased hypoxia, this physiological characteristic is considered as highly unfavorable for melanoma prognosis and therapy outcome. Lymphangiogenesis, by contrast, was not influenced by EphB4 overexpression. In order to distinguish between EphB4 forward and EphrinB2, the natural EphB4 ligand, reverse signaling a specific EphB4 kinase inhibitor was applied. Blocking experiments show EphrinB2 reverse signaling rather than EphB4 forward signaling to be responsible fo...Continue Reading

References

Jan 1, 1992·International Journal of Radiation Oncology, Biology, Physics·W J KohT W Griffin
Mar 1, 1988·British Journal of Cancer·K A SmithJ Denekamp
Dec 1, 1985·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C S Patlak, R G Blasberg
Nov 18, 1971·The New England Journal of Medicine·J Folkman
Feb 26, 1999·The Journal of Cell Biology·S BanerjiD G Jackson
Jan 11, 2001·Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T·N MullaniK Gould
Feb 24, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S UgurelU Reinhold
May 30, 2001·Trends in Immunology·D G JacksonS Banerji
Jan 22, 2002·BMC Molecular Biology·S A StephensonJ E Hardingham
Mar 29, 2002·Cancer·Wenbiao LiuLee M Ellis
Apr 27, 2002·Science·Timothy P PaderaRakesh K Jain
Feb 4, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G BerclazA-C Andres
May 22, 2003·The American Journal of Pathology·Soheil S DadrasMichael Detmar
Jun 6, 2003·Oncogene·Michael Streit, Michael Detmar
Apr 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicole K NorenElena B Pasquale
Apr 15, 2004·British Journal of Cancer·W LiuL M Ellis
May 12, 2004·Nature Reviews. Drug Discovery·Napoleone FerraraWilliam Novotny
Feb 3, 2005·Genes & Development·Taija MäkinenGeorge A Wilkinson
Apr 2, 2005·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Soheil S DadrasMichael Detmar
Jul 4, 2006·The American Journal of Pathology·S Ram KumarParkash S Gill
Jul 25, 2006·Nature Reviews. Cancer·Andrew I Minchinton, Ian F Tannock
Feb 28, 2007·Radiology·Xavier MontetRalph Weissleder
Mar 27, 2007·Nuclear Medicine and Biology·Mark A GreenGary D Hutchins
May 8, 2007·Cancer Research·Nicole K Noren, Elena B Pasquale
Mar 18, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nizar A MullaniJames L Abbruzzese
Mar 22, 2008·Nuclear Medicine and Biology·Nathan E BaskenMark A Green
May 16, 2008·Journal of Cellular Physiology·Matthias Rinderknecht, Michael Detmar
Jan 23, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Roger MouawadDavid Khayat
Feb 26, 2009·British Journal of Cancer·J A NagyH F Dvorak
Jun 13, 2009·Current Molecular Medicine·Sara RockwellVan Thuc Vu
Jul 9, 2009·Journal of Cellular and Molecular Medicine·Viviane Mumprecht, Michael Detmar
Aug 22, 2009·Cancer Biotherapy & Radiopharmaceuticals·Carolyn J Anderson, Riccardo Ferdani

❮ Previous
Next ❯

Citations

Jul 11, 2018·Angiogenesis·Christian UhlMarcus Czabanka
Mar 23, 2021·Frontiers in Oncology·Camille FuselierChristophe Schneider
Nov 7, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christin NeuberJens Pietzsch

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
xenografts
transgenic
fluorescence imaging
fluorescence microscopy
transfection
flow cytometry
reverse transcription-PCR
electrophoresis
ELISA

Software Mentioned

ROVER
Bruker Molecular Imaging
Total Lab
Fiji
OriginPro
AxioVision
R environment for

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.