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Review Article

Targeting glioma stem cells via the Hedgehog

signaling pathway

Yang Liu, Xing Liu, Ling‑Chao Chen, Wen‑Zhong Du, Yu‑Qiong Cui, Xing‑Yin Piao, Yong‑Li Li, Chuan‑Lu Jiang
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China.

ABSTRA CT
Cancer is one of the leading causes of death worldwide. Gliomas are among the most devastating tumor types, and current clinical
therapies are unsatisfactory. Recent reports revealed the importance of glioma‑propagating cells in the malignancy of gliomas. These
cells, also referred to as glioma stem cells (GSCs), share similarities with neural stem cells (NSCs). The Hedgehog (Hh) signaling
pathway controls tissue polarity, patterning maintenance, and maintenance of NSCs during embryonic development. Aberrant
activation of the Hh pathway resulting from mutation and deregulation has recently been recognized to cause tumorigenesis in a
wide variety of tissues, including gliomas and GSCs. In this review, we explore the role of the Hh signaling pathway in GSCs and
its potential as a therapeutic strategy.

Key words: Cancer stem cells, glioma, Hedgehog, microRNA

INTRODUCTION and maintenance of glioma stem cells (GSCs). Since
[4]
GSCs are important biological factors responsible
Cancer is estimated to be the leading cause of death for cancer invasion, metastasis, drug resistance, and
worldwide by the World Health Organization (WHO). relapse, Hh signaling is believed to be an important
[1]
Gliomas are one of the most lethal adult brain tumors. target for cancer therapy. Recently, both natural and
Although substantial progress has been made, there synthesized small-molecule inhibitors of Hh signaling
is still a lack of effective therapy. It is reported that have been investigated as potential cancer treatments.
patients with low-grade gliomas can survive for years, However, targeting only one molecule may be
while patients with glioblastoma (WHO grade IV) insufficient. Therefore, strategies using a combination
survive for only 1-2 years after diagnosis. [2] of natural products and chemotherapeutics with
different targets may improve the overall survival of
Tumors are composed of a heterogeneous group of patients with gliomas.
cells. Some tumor cell fractions have the ability to
initiate tumors in xenograft models, whereas other CANCER STEM CELLS IN GLIOMA
fractions do not. These cells, capable of sphere-like
[3]
growth in vitro and tumor formation in vivo, are defined Cancer stem cells and the niche
as cancer stem cells (CSCs) and share similarities The concept of CSCs has been in use for over 50 years.
with normal neural stem cells (NSCs). It has been In the 1990s, Lapidot et al. identified leukemia stem
[5]
hypothesized that these cells are involved in radio- and cells capable of generating human acute myeloid
chemo-resistance, as well as tumor recurrence. leukemia after transplantation. Within gliomas, stem-
like cells with the ability to self-renew, differentiate
The Hedgehog (Hh) signaling pathway plays a pivotal into multiple lineages, and initiate tumors are known as
role in embryonic development, including the formation GSCs. Subsequently, GSCs capable of self-renewal and
producing glioma-initiating cells were identified using
Access this article online a limiting dilution analysis. The presence of GSCs and
[6]
Quick Response Code: the increasing evidence of radio-resistance and chemo-
Website: resistance indicated that GSCs may contribute to tumor
www.nnjournal.net
maintenance and recurrence, and that targeting GSCs
DOI: may be a promising therapeutic intervention. [7,8] Stem
10.4103/2347-8659.139715 cells reside in specialized niches, which could regulate
their proliferation and differentiation. More than one
[9]
Corresponding Author: Dr. Chuan‑Lu Jiang, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical
University, No. 246 Xuefu Road, Nangang, Harbin 150086, Heilongjiang, China. E‑mail: jcl6688@163.com

Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014 51