Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2

The Journal of Clinical Investigation
Peter VajkoczyG Breier

Abstract

Tumors have been thought to initiate as avascular aggregates of malignant cells that only later induce vascularization. Recently, this classic concept of tumor angiogenesis has been challenged by the suggestion that tumor cells grow by co-opting preexisting host vessels and thus initiate as well-vascularized tumors without triggering angiogenesis. To discriminate between these two mechanisms, we have used intravital epifluorescence microscopy and multi-photon laser scanning confocal microscopy to visualize C6 microglioma vascularization and tumor cell behavior. To address the mechanisms underlying tumor initiation, we assessed the expression of VEGF, VEGF receptor-2 (VEGFR-2), and angiopoietin-2 (Ang-2), as well as endothelial cell proliferation. We show that multicellular aggregates (< 1 mm(3)) initiate vascular growth by angiogenic sprouting via the simultaneous expression of VEGFR-2 and Ang-2 by host and tumor endothelium. Host blood vessels are not co-opted by tumor cells but rather are used as trails for tumor cell invasion of the host tissue. Our data further suggest that the established microvasculature of growing tumors is characterized by a continuous vascular remodeling, putatively mediated by the expression of VEGF a...Continue Reading

References

Nov 18, 1971·The New England Journal of Medicine·J Folkman
Aug 1, 1972·The Journal of Experimental Medicine·M A GimbroneJ Folkman
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·D ShweikiE Keshet
May 20, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·P VajkoczyM D Menger
Mar 31, 1999·Methods in Molecular Biology·G Breier
Sep 24, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·N Ferrara
Nov 26, 1999·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·P VajkoczyM D Menger
Jan 20, 2000·Journal of the National Cancer Institute·C Y LiM W Dewhirst
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·P VajkoczyM D Menger
Sep 23, 2000·Nature·G D YancopoulosJ Holash
Apr 3, 2001·Nature Reviews. Molecular Cell Biology·N JonesK Alitalo

❮ Previous
Next ❯

Citations

May 8, 2010·Angiogenesis·T J A SnoeksE L Kaijzel
Aug 23, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D RibattiF Dammacco
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Peter VajkoczyAxel Ullrich
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yuan XueYihai Cao
Sep 19, 2009·The Journal of Biological Chemistry·Qiangming SunJohn R Basile
Jun 18, 2003·The Journal of Experimental Medicine·Peter VajkoczyAntonis K Hatzopoulos
Aug 25, 2010·Investigative Radiology·Christopher R AndersonAlexander L Klibanov
Mar 10, 2010·Journal of Biomedical Optics·Sarah Jane LuntGillian M Tozer
Jul 2, 2010·Journal of Oncology·Paloma Sanz-CamenoRicardo Moreno-Otero
Oct 7, 2011·Journal of Oncology·William W LiAlbert S Chiou
Jun 4, 2010·PloS One·Robert C CastellinoDonald L Durden
Feb 15, 2014·Journal of Cancer Research and Clinical Oncology·Jie ZhangYu Jiang
May 23, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yue JinYu Wang
Oct 20, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Keith M StantzKathy D Miller
Sep 29, 2006·Cancer Metastasis Reviews·Gera Neufeld, Ofra Kessler
May 29, 2013·Cell Biochemistry and Biophysics·Xing-Yu HongZhe Li
Feb 8, 2008·Current Treatment Options in Oncology·David A ReardonJames J Vredenburgh
Mar 21, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yasushi SodaInder M Verma
Sep 10, 2013·Surgical Oncology Clinics of North America·Jennifer SamplesNancy Klauber-Demore
Aug 7, 2010·Bone·T J A SnoeksC W G M Löwik
Mar 6, 2008·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Markus DehnhardtAndreas Bauer
May 4, 2007·NeuroImage·Hermann B FrieboesVittorio Cristini
Feb 13, 2007·Experimental Cell Research·Christiana CharalambousFlorence M Hofman
Feb 23, 2007·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·O KollmarM K Schilling
Sep 24, 2008·Alimentary Pharmacology & Therapeutics·M ChaparroR Moreno-Otero
Nov 19, 2011·Journal of Cellular Biochemistry·Cara F BuchananMarissa Nichole Rylander
Feb 14, 2014·Brain Pathology·Linda PilgaardMeg Duroux
Sep 19, 2003·Biochemical and Biophysical Research Communications·Mingqing CaiRutai Hui
Jun 24, 2004·Brain Research. Brain Research Reviews·Marnix JansenCornelis J F van Noorden
Jul 25, 2006·Critical Reviews in Oncology/hematology·J TuettenbergP Vajkoczy
Aug 2, 2006·Cancer Letters·Domenico RibattiAngelo Vacca
Mar 23, 2005·Critical Reviews in Oncology/hematology·Patrick AugusteAndreas Bikfalvi
Jun 3, 2015·Biology of the Cell·Kinga G BlecharzPeter Vajkoczy

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

CNS Lymphoma

In CNS lymphoma, cancerous cells from lymph tissues or other parts of the body form tumors in the brain and/or spinal cord. Here is the latest research on this rare non-Hodgkin lymphoma.