ReviewHyaluronan: A constitutive regulator of chemoresistance and malignancy in cancer cells
Section snippets
Introduction: the relationships between drug resistance, malignancy and cancer stem-like cells
Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of morbidity and mortality from cancer. Recently, sub-populations of stem-like cells have been characterized within a variety of cancers. These cells are highly malignant in that they can rapidly regenerate a fully grown tumor when implanted in small numbers in an animal host [1], [2], [3] and they may be responsible for tumor metastasis [4], [5]. In addition, these cells
Hyaluronan in tumor progression
Hyaluronan is a large, linear glycosaminoglycan composed of 2000–25,000 disaccharides of glucuronic acid and N-acetylglucosamine: [β1,4-GlcUA-β1,3-GlcNAc-]n, with molecular weights usually ranging from 105 to 107 Da. Hyaluronan is distributed ubiquitously in vertebrate tissues. In adult tissues such as the vitreous, synovial fluid and dermis, it clearly plays an extracellular, structural role that depends on its unique hydrodynamic properties as well as its interactions with other extracellular
Cell autonomous regulation of receptor tyrosine kinase activation and anti-apoptotic signaling pathways by endogenously produced hyaluronan
Receptor tyrosine kinases are a class of plasma membrane receptors that bind various regulatory factors, such as EGF, IGF, HGF and PDGF, and activate several intracellular signaling pathways, such as the MAP kinase and phosphoinositide 3-kinase/AKT pathways. Aberrant activities of these receptors, especially members of the ERBB family, have been implicated in the progression of numerous types of human cancers. Increased activity of receptor tyrosine kinases can arise from gene amplification,
Regulation of multidrug resistance by hyaluronan
Drug resistance can arise in numerous ways, e.g. decreased uptake of drugs due to cell and tissue barriers, activation of repair and detoxification mechanisms, increased activities of anti-apoptotic signaling pathways, or enhanced drug efflux via cell membrane transporters [59], [60], [61], [62]. Drug efflux from cancer cells is commonly mediated by ATP-dependent efflux pumps such as members of the MDR, MRP and other ABC transporter subgroups, and expression of these transporters is frequently
Hyaluronan–CD44 interactions, cancer stem cells and resistance to chemotherapy
Of particular relevance to the relationship of malignant cell properties to chemoresistance are the properties of a small sub-population of stem-like cells that has now been characterized within many cancers. These cells have been variously named: “cancer stem cells”, “cancer progenitor cells” and “tumor-initiating cells”. These cells are highly malignant in that a very small number can rapidly regenerate a fully grown tumor when implanted in an animal host [1], [2], [3] and they may include
Acknowledgements
Recent work from our lab that is described herein was supported by grants to B.P.T. from the National Institutes of Health (CA073839 and CA082867), the Department of Defense (OC050368) and The Charlotte Geyer Foundation.
References (105)
- et al.
Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2
J Biol Chem
(2005) - et al.
The multidrug transporter P-glycoprotein: a mediator of melanoma invasion?
J Invest Dermatol
(2008) - et al.
The impact of extracellular matrix on the chemoresistance of solid tumors—experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy
Cancer Lett
(1998) - et al.
Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters
Biochem Pharmacol
(2004) Hyaluronan in morphogenesis
Semin Cell Dev Biol
(2001)- et al.
Signaling properties of hyaluronan receptors
J Biol Chem
(2002) - et al.
Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways
Matrix Biol
(2007) - et al.
Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: possible involvement of versican/PG-M
Am J Pathol
(2007) - et al.
Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice
Am J Pathol
(2002) - et al.
Perturbation of hyaluronan interactions by soluble CD44 inhibits growth of murine mammary carcinoma cells in ascites
Am J Pathol
(2000)