Vascular heterogeneity and targeting: the role of YKL-40 in glioblastoma vascularization

Rong Shao, Sherry L. Taylor, Dennis S. Oh and Lawrence M. Schwartz _

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Oncotarget. 2015; 6:40507-40518. https://doi.org/10.18632/oncotarget.5943

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Rong Shao1,2, Sherry L. Taylor3, Dennis S. Oh4 and Lawrence M. Schwartz1,2

1 Department of Biology, University of Massachusetts, Amherst, MA, USA

2 Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA, USA

3 Department of Neurosurgery, Tufts University, Boston, MA, USA

4 Department of Surgery, Baystate Medical Center, Tufts University, Springfield, MA, USA

Correspondence to:

Rong Shao, email:

Lawrence M. Schwartz, email:

Keywords: glioblastoma, YKL-40, glioblastoma stem-like cells, transdifferentiation, tumor angiogenesis

Received: July 22, 2015 Accepted: September 14, 2015 Published: October 01, 2015


Malignant glioblastomas (GBM) are highly malignant brain tumors that have extensive and aberrant tumor vasculature, including multiple types of vessels. This review focuses on recent discoveries that the angiogenic factor YKL-40 (CHI3L1) acts on glioblastoma-stem like cells (GSCs) to drive the formation of two major forms of tumor vascularization: angiogenesis and vasculogenic mimicry (VM). GSCs possess multipotent cells able to transdifferentiate into vascular pericytes or smooth muscle cells (PC/SMCs) that either coordinate with endothelial cells (ECs) to facilitate angiogenesis or assemble in the absence of ECs to form blood-perfused channels via VM. GBMs express high levels of YKL-40 that drives the divergent signaling cascades to mediate the formation of these distinct microvascular circulations. Although a variety of anti-tumor agents that target angiogenesis have demonstrated transient benefits for patients, they often fail to restrict tumor growth, which underscores the need for additional therapeutic tools. We propose that targeting YKL-40 may compliment conventional anti-angiogenic therapies to provide a substantial clinical benefit to patients with GBM and several other types of solid tumors.

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