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BioMed Research International
Volume 2014, Article ID 986768, 8 pages
Review Article

From Sprouting Angiogenesis to Erythrocytes Generation by Cancer Stem Cells: Evolving Concepts in Tumor Microcirculation

Division of Hematology and Oncology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut 1107-2020, Lebanon

Received 9 May 2014; Revised 13 July 2014; Accepted 14 July 2014; Published 4 August 2014

Academic Editor: Shiwu Zhang

Copyright © 2014 Raafat S. Alameddine et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Angiogenesis is essential for tumor growth and metastasis. Over the last decades, a substantial progress has been achieved in defining different patterns of tumor microcirculation. Sprouting angiogenesis, the oldest model of microcirculation, is the de novo vessel formation from preexisting blood vessels. Vessel splitting and hijacking, also known, respectively, as intussusception and cooption, are alternative models that account for tumor resistance to antiangiogenic therapy. In addition to remodeling the microenvironment, the tumor cell can undergo intrinsic changes and survive hypoxic conditions by acquiring stem cell properties. In line with the concept of pluripotency, tumor cells can form vascular mimicry structures creating their own microcirculation despite a latent vessel growth. The recent identification of the polyploid giant cancer cells and tumor-derived erythrocytes is the most innovative survival mechanism in hypoxia and provides a potential target for more effective therapies.