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Review
. 2014:123:255-75.
doi: 10.1016/B978-0-12-800092-2.00010-1.

Hyaluronan-CD44 interaction promotes oncogenic signaling, microRNA functions, chemoresistance, and radiation resistance in cancer stem cells leading to tumor progression

Lilly Y W Bourguignon  1 , Marisa Shiina  2 , Jian-Jian Li  3
Affiliations
Review

Hyaluronan-CD44 interaction promotes oncogenic signaling, microRNA functions, chemoresistance, and radiation resistance in cancer stem cells leading to tumor progression

Lilly Y W Bourguignon et al. Adv Cancer Res. 2014.

Abstract

Hyaluronan (HA), a major component of the extracellular matrix (ECM), is enriched in many types of tumors. There is good evidence linking high levels of HA production in human carcinomas to an aggressive phenotype and tumor metastasis. HA is generally bound to CD44 isoforms (so-called CD44s and CD44v3) which are ubiquitous, abundant, and functionally important cell surface receptors. This chapter describes the evidence for HA/CD44v3-mediated activation of the cytoskeleton (e.g., ankyrin and GTPases) and matrix metalloproteinase (MMP) signaling during tumor progression. A special focus is placed on the role of HA-CD44v3 interaction in cancer stem cells (CSCs). Matrix HA is known to be present in CSC niches. Since CD44v3 serves as a CSC marker, it provides an important physical linkage between matrix HA and various transcription factors that regulate tumor cell functions through distinct signaling pathways. CSCs are known to be chemoresistant and/or radiation resistant and to cause cancer relapse. The purpose of this chapter is to review the most current research on the cellular and molecular biology of CSCs. The emphasis will be placed on both CSC niche and matrix HA-induced microRNA signaling plus various CSC functions (e.g., self-renewal, differentiation, and chemoresistance) during cancer progression. Understanding the regulation of CSCs is critically important for designing CSC-specific therapeutic targets to prevent cancer development and progression.

Keywords: CD44; Cancer stem cells; Chemoresistance; Matrix hyaluronan; Radiation resistance; Tumor progression; microRNAs.

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Figures

Figure 10.1
Figure 10.1
Immunoperoxidase staining of CD44 in human primary breast tumor and lymph node metastasis samples.
Figure 10.2
Figure 10.2
A proposed model for HA/CD44-mediated RhoGTPase signaling and cytoskeleton-mediated functions.
Figure 10.3
Figure 10.3
HA/CD44-mediated sphere formation (A) and stem cell marker expression in sphere cells with multiple generations of passages (B).
Figure 10.4
Figure 10.4
A proposed model for cancer stem cell signaling and tumor progression.
See this image and copyright information in PMC

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