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PMID: 18490190 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Hyaluronan, CD44 and Emmprin: partners in cancer cell chemoresistance.

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy ·Vol. 11 ·No. 3 ·2008-06-00 ·Pages 110-21

Toole BP, Slomiany MG

Abstract

Hyaluronan not only is an important structural component of extracellular matrices but also interacts with cells during dynamic cell processes such as those occurring in cancer. Consequently, interactions of hyaluronan with tumor cells play important cooperative roles in various aspects of malignancy. Hyaluronan binds to several cell surface receptors, including CD44, thus leading to co-regulation of signaling pathways that are important in regulation of multidrug resistance to anticancer drugs, in particular anti-apoptotic pathways induced by activation of receptor tyrosine kinases. Emmprin, a cell surface glycoprotein of the Ig superfamily, stimulates hyaluronan production and downstream signaling consequences. Emmprin and CD44 also interact with various multidrug transporters of the ABC family and monocarboxylate transporters associated with resistance to cancer therapies. Moreover, hyaluronan-CD44 interactions are critical to these properties in the highly malignant, chemotherapy-resistant cancer stem-like cells. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo. These antagonists, especially small hyaluronan oligomers, may be useful in therapeutic strategies aimed at preventing tumor refractoriness or recurrence due to drug-resistant sub-populations within malignant cancers.

MeSH Terms
ATP-Binding Cassette Transporters/metabolism Antineoplastic Agents/pharmacology Apoptosis/physiology Basigin/physiology Cell Membrane/metabolism Cell Survival/physiology Drug Resistance, Neoplasm/physiology Humans Hyaluronan Receptors/physiology Hyaluronic Acid/physiology Monocarboxylic Acid Transporters/metabolism Neoplasms/genetics,metabolism Phenotype Signal Transduction
Chemicals
ATP-Binding Cassette Transporters Antineoplastic Agents Hyaluronan Receptors Monocarboxylic Acid Transporters Basigin Hyaluronic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Toole Bryan P
Department of Cell Biology and Anatomy, Medical University of South Carolina, USA. toolebp@musc.edu
Slomiany Mark G
References (156)
156 references, click to expand
  1. cGMP transport by vesicles from human and mouse erythrocytes.
    FEBS J. 2007 Jan;274(2):439-50 PMID: 17229149
  2. The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.
    Mol Pharmacol. 2006 Dec;70(6):2108-15 PMID: 17000864
  3. Reversal of intrinsic and acquired forms of drug resistance by hyaluronidase treatment of solid tumors.
    Cancer Lett. 1998 Sep 11;131(1):35-44 PMID: 9839618
  4. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
    Cancer Res. 2006 Jan 15;66(2):632-7 PMID: 16423989
  5. Hyaluronan binding by cell surface CD44.
    J Biol Chem. 2000 Sep 1;275(35):26967-75 PMID: 10871609
  6. The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer.
    Cancer Res. 2005 Aug 1;65(15):6660-7 PMID: 16061646
  7. Targeting of CD44 eradicates human acute myeloid leukemic stem cells.
    Nat Med. 2006 Oct;12(10):1167-74 PMID: 16998484
  8. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow.
    Blood. 2004 Apr 15;103(8):2981-9 PMID: 15070674
  9. Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70).
    J Biol Chem. 2005 Jul 22;280(29):27213-21 PMID: 15917240
  10. Potential role for hyaluronan and the hyaluronan receptor RHAMM in mobilization and trafficking of hematopoietic progenitor cells.
    Blood. 1999 May 1;93(9):2918-27 PMID: 10216086
  11. Glucose starvation and acidosis: effect on experimental metastatic potential, DNA content and MTX resistance of murine tumour cells.
    Br J Cancer. 1991 Oct;64(4):663-70 PMID: 1911214
  12. Characterization of hyaluronan synthase expression and hyaluronan synthesis in bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and up-regulated hyaluronan synthesis in bone marrow cells derived from multiple myeloma patients.
    Blood. 2002 Oct 1;100(7):2578-85 PMID: 12239172
  13. Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth.
    J Biol Chem. 2001 Dec 28;276(52):48679-92 PMID: 11606575
  14. Tumor microenvironment and drug resistance in hematologic malignancies.
    Blood Rev. 2006 Nov;20(6):333-42 PMID: 16920238
  15. Phenotypic characterization of human colorectal cancer stem cells.
    Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63 PMID: 17548814
  16. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells.
    Nat Med. 2006 Oct;12(10):1175-80 PMID: 16998483
  17. Hyaluronan synthases: a decade-plus of novel glycosyltransferases.
    J Biol Chem. 2007 Dec 21;282(51):36777-81 PMID: 17981795
  18. RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma.
    Blood. 2004 Aug 15;104(4):1151-8 PMID: 15105292
  19. "Destemming" cancer stem cells.
    J Natl Cancer Inst. 2007 Oct 3;99(19):1435-40 PMID: 17895479
  20. Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function.
    J Exp Med. 1997 Dec 15;186(12):1985-96 PMID: 9396767
  21. Perturbation of hyaluronan interactions by soluble CD44 inhibits growth of murine mammary carcinoma cells in ascites.
    Am J Pathol. 2000 Jun;156(6):2159-67 PMID: 10854236
  22. Molecular features, regulation, and function of monocarboxylate transporters: implications for drug delivery.
    J Pharm Sci. 2003 Aug;92(8):1531-44 PMID: 12884241
  23. The discovery of receptor tyrosine kinases: targets for cancer therapy.
    Nat Rev Cancer. 2004 May;4(5):361-70 PMID: 15122207
  24. Why do cancers have high aerobic glycolysis?
    Nat Rev Cancer. 2004 Nov;4(11):891-9 PMID: 15516961
  25. Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44.
    J Biol Chem. 2006 Sep 8;281(36):26512-9 PMID: 16809345
  26. Different CD44 splicing patterns define prognostic subgroups in multiple myeloma.
    Blood. 1996 Oct 15;88(8):3101-8 PMID: 8874209
  27. Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of human breast carcinomas: comparison between invasive and non-invasive areas.
    Int J Cancer. 1992 Aug 19;52(1):1-6 PMID: 1379993
  28. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.
    J Clin Invest. 2003 Mar;111(5):627-37 PMID: 12618517
  29. Tumour stem cells and drug resistance.
    Nat Rev Cancer. 2005 Apr;5(4):275-84 PMID: 15803154
  30. Effects of detergent solubilization on the hyaluronate-binding protein from membranes of simian virus 40-transformed 3T3 cells.
    J Biol Chem. 1983 Jul 10;258(13):8086-91 PMID: 6190806
  31. Chemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44-hyaluronan binding.
    J Cell Sci. 2005 Nov 1;118(Pt 21):5119-28 PMID: 16234326
  32. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells.
    Cancer Res. 2007 May 15;67(10):4827-33 PMID: 17510412
  33. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases.
    Cancer Res. 2005 Apr 15;65(8):3193-9 PMID: 15833850
  34. Akt signaling regulates side population cell phenotype via Bcrp1 translocation.
    J Biol Chem. 2003 Oct 3;278(40):39068-75 PMID: 12851395
  35. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  36. Autophagy signaling in cancer and its potential as novel target to improve anticancer therapy.
    Drug Resist Updat. 2007 Aug-Oct;10(4-5):135-43 PMID: 17627865
  37. The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells.
    J Biol Chem. 2007 Jun 1;282(22):16667-80 PMID: 17392272
  38. Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice.
    Am J Pathol. 2002 Sep;161(3):849-57 PMID: 12213713
  39. Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse.
    Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1305-11 PMID: 12601063
  40. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.
    Cell. 1991 Apr 5;65(1):13-24 PMID: 1707342
  41. Cancer stem cells: models and concepts.
    Annu Rev Med. 2007;58:267-84 PMID: 17002552
  42. Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ.
    J Biol Chem. 2002 Feb 1;277(5):3666-72 PMID: 11719518
  43. Untangling the ErbB signalling network.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 PMID: 11252954
  44. CD44 in cancer progression: adhesion, migration and growth regulation.
    J Mol Histol. 2004 Mar;35(3):211-31 PMID: 15339042
  45. Signaling properties of hyaluronan receptors.
    J Biol Chem. 2002 Feb 15;277(7):4589-92 PMID: 11717317
  46. Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential.
    Cancer Res. 1983 Mar;43(3):1347-54 PMID: 6825105
  47. Human mesothelioma cells produce factors that stimulate the production of hyaluronan by mesothelial cells and fibroblasts.
    Cancer Res. 1993 Jan 15;53(2):388-92 PMID: 8417831
  48. CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion.
    J Biol Chem. 2004 Jun 25;279(26):26991-7007 PMID: 15090545
  49. Raft and cytoskeleton associations of an ABC transporter: P-glycoprotein.
    Cytometry A. 2004 Oct;61(2):105-16 PMID: 15382145
  50. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
    Pflugers Arch. 2004 Feb;447(5):619-28 PMID: 12739169
  51. Hyaluronan, a major non-protein glycosaminoglycan component of the extracellular matrix in human bone marrow, mediates dexamethasone resistance in multiple myeloma.
    Br J Haematol. 2003 Apr;121(2):259-69 PMID: 12694247
  52. Are CD44 variant isoforms involved in human tumour progression?
    Cancer Surv. 1995;24:19-42 PMID: 7553660
  53. Hyaluronan-dependent pericellular matrix.
    Adv Drug Deliv Rev. 2007 Nov 10;59(13):1351-65 PMID: 17804111
  54. Hyaluronan: from extracellular glue to pericellular cue.
    Nat Rev Cancer. 2004 Jul;4(7):528-39 PMID: 15229478
  55. Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB.
    Biochem J. 2007 Jun 1;404(2):327-36 PMID: 17324121
  56. Lactate-sensitive response elements in genes involved in hyaluronan catabolism.
    Biochem Biophys Res Commun. 2003 May 23;305(1):203-8 PMID: 12732217
  57. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic.
    Cancer Res. 2005 Jul 15;65(14):6207-19 PMID: 16024622
  58. Hyaluronan enters keratinocytes by a novel endocytic route for catabolism.
    J Biol Chem. 2001 Sep 14;276(37):35111-22 PMID: 11451952
  59. Multidrug resistance in cancer: role of ATP-dependent transporters.
    Nat Rev Cancer. 2002 Jan;2(1):48-58 PMID: 11902585
  60. Molecular definition of breast tumor heterogeneity.
    Cancer Cell. 2007 Mar;11(3):259-73 PMID: 17349583
  61. Beyond tumorigenesis: cancer stem cells in metastasis.
    Cell Res. 2007 Jan;17(1):3-14 PMID: 17179981
  62. Receptors for hyaluronate on the surface of parent and virus-transformed cell lines: binding and aggregation studies.
    Exp Cell Res. 1981 Feb;131(2):419-23 PMID: 7202543
  63. CD44 promotes resistance to apoptosis in human colon cancer cells.
    Exp Mol Pathol. 2004 Aug;77(1):18-25 PMID: 15215046
  64. Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion.
    Mol Cell Biol. 2006 Jan;26(1):362-70 PMID: 16354706
  65. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons.
    J Cell Biol. 1994 Jul;126(2):391-401 PMID: 7518464
  66. CD44-mediated uptake and degradation of hyaluronan.
    Matrix Biol. 2002 Jan;21(1):15-23 PMID: 11827788
  67. The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis.
    Drug Resist Updat. 2006 Aug-Oct;9(4-5):227-46 PMID: 17092765
  68. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma.
    Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8 PMID: 17210912
  69. Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid.
    Oncogene. 2001 Jun 7;20(26):3399-408 PMID: 11423990
  70. Hyaluronan-binding proteins: tying up the giant.
    J Biol Chem. 2002 Feb 15;277(7):4585-8 PMID: 11717315
  71. Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration.
    J Biol Chem. 2007 Jul 6;282(27):19426-41 PMID: 17493932
  72. SP analysis may be used to identify cancer stem cell populations.
    Exp Cell Res. 2006 Nov 15;312(19):3701-10 PMID: 17046749
  73. Tumour-initiating cells vs. cancer 'stem' cells and CD133: what's in the name?
    Biochem Biophys Res Commun. 2007 Apr 20;355(4):855-9 PMID: 17307142
  74. Hyaluronan is synthesized by primitive hemopoietic cells, participates in their lodgment at the endosteum following transplantation, and is involved in the regulation of their proliferation and differentiation in vitro.
    Blood. 2003 Feb 1;101(3):856-62 PMID: 12393456
  75. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme.
    J Clin Invest. 2000 Aug;106(3):349-60 PMID: 10930438
  76. Regulation of multidrug resistance in cancer cells by hyaluronan.
    J Biol Chem. 2003 Jul 11;278(28):25285-8 PMID: 12738783
  77. A case study in misidentification of cancer cell lines: MCF-7/AdrR cells (re-designated NCI/ADR-RES) are derived from OVCAR-8 human ovarian carcinoma cells.
    Cancer Lett. 2007 Jan 8;245(1-2):350-2 PMID: 16504380
  78. Tumour regulation of fibroblast hyaluronan expression: a mechanism to facilitate tumour growth and invasion.
    Carcinogenesis. 2005 Jul;26(7):1215-23 PMID: 15746159
  79. Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: possible involvement of versican/PG-M.
    Am J Pathol. 2007 Mar;170(3):1086-99 PMID: 17322391
  80. Targeting multiple arms of the apoptotic regulatory machinery.
    Cancer Res. 2007 Apr 1;67(7):2908-11 PMID: 17409392
  81. 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 Sep 11;131(1):85-99 PMID: 9839623
  82. A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells.
    Cancer Res. 2001 Jul 1;61(13):5275-83 PMID: 11431370
  83. Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways.
    Matrix Biol. 2007 Jan;26(1):58-68 PMID: 17055233
  84. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles.
    Cancer Res. 2007 May 1;67(9):4010-5 PMID: 17483311
  85. Cancer stem cells in solid tumors.
    Curr Opin Biotechnol. 2007 Oct;18(5):460-6 PMID: 18023337
  86. Hyaluronan oligosaccharides inhibit anchorage-independent growth of tumor cells by suppressing the phosphoinositide 3-kinase/Akt cell survival pathway.
    J Biol Chem. 2002 Oct 11;277(41):38013-20 PMID: 12145277
  87. The role and regulation of tumour-associated hyaluronan.
    Ciba Found Symp. 1989;143:150-9; discussion 159-69, 281-5 PMID: 2680343
  88. Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors.
    Clin Cancer Res. 2008 Mar 15;14(6):1804-13 PMID: 18347183
  89. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression.
    Thromb Haemost. 2005 Feb;93(2):199-204 PMID: 15711733
  90. CD44 involvement in autoimmune inflammations: the lesson to be learned from CD44-targeting by antibody or from knockout mice.
    Ann N Y Acad Sci. 2007 Sep;1110:233-47 PMID: 17911438
  91. Tyrosine kinases as targets for cancer therapy.
    N Engl J Med. 2005 Jul 14;353(2):172-87 PMID: 16014887
  92. Brain tumour stem cells.
    Nat Rev Cancer. 2006 Jun;6(6):425-36 PMID: 16723989
  93. The multidrug transporter P-glycoprotein: a mediator of melanoma invasion?
    J Invest Dermatol. 2008 Apr;128(4):957-71 PMID: 17943188
  94. The Akt/PKB pathway: molecular target for cancer drug discovery.
    Oncogene. 2005 Nov 14;24(50):7482-92 PMID: 16288295
  95. Metabolic activation-related CD147-CD98 complex.
    Mol Cell Proteomics. 2005 Aug;4(8):1061-71 PMID: 15901826
  96. Multicellular resistance: a paradigm for clinical resistance?
    Crit Rev Oncol Hematol. 2000 Nov-Dec;36(2-3):193-207 PMID: 11033306
  97. Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters.
    Biochem Pharmacol. 2004 Oct 1;68(7):1401-10 PMID: 15345330
  98. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression.
    EMBO J. 2000 Aug 1;19(15):3896-904 PMID: 10921872
  99. A positive feedback loop couples Ras activation and CD44 alternative splicing.
    Genes Dev. 2006 Jul 1;20(13):1715-20 PMID: 16818603
  100. CD44 and hematologic malignancies.
    Cell Mol Immunol. 2006 Oct;3(5):359-65 PMID: 17092433
  101. Hyaluronan in tissue injury and repair.
    Annu Rev Cell Dev Biol. 2007;23:435-61 PMID: 17506690
  102. Drug resistance and the solid tumor microenvironment.
    J Natl Cancer Inst. 2007 Oct 3;99(19):1441-54 PMID: 17895480
  103. Hyaluronan constitutively regulates ErbB2 phosphorylation and signaling complex formation in carcinoma cells.
    J Biol Chem. 2005 Mar 11;280(10):8875-83 PMID: 15632176
  104. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.
    Nat Rev Cancer. 2005 Sep;5(9):744-9 PMID: 16148886
  105. Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma.
    Blood. 2005 Jun 15;105(12):4836-44 PMID: 15731173
  106. Hyaluronate and invasiveness of the rabbit V2 carcinoma.
    Proc Natl Acad Sci U S A. 1979 Dec;76(12):6299-303 PMID: 293721
  107. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions.
    Cancer Res. 2001 Mar 1;61(5):2276-81 PMID: 11280798
  108. Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs.
    Drug Resist Updat. 2007 Feb-Apr;10(1-2):59-67 PMID: 17350322
  109. The proteasome as a potential target for novel anticancer drugs and chemosensitizers.
    Drug Resist Updat. 2006 Dec;9(6):263-73 PMID: 17197231
  110. Hyaluronan-cell interactions in cancer and vascular disease.
    J Biol Chem. 2002 Feb 15;277(7):4593-6 PMID: 11717318
  111. Acidic pH enhances the invasive behavior of human melanoma cells.
    Clin Exp Metastasis. 1996 Mar;14(2):176-86 PMID: 8605731
  112. Emmprin promotes anchorage-independent growth in human mammary carcinoma cells by stimulating hyaluronan production.
    Cancer Res. 2004 Feb 15;64(4):1229-32 PMID: 14983875
  113. Glycolysis inhibition for anticancer treatment.
    Oncogene. 2006 Aug 7;25(34):4633-46 PMID: 16892078
  114. Activation of the MDR1 upstream promoter in breast carcinoma as a surrogate for metastatic invasion.
    Clin Cancer Res. 2004 Apr 15;10(8):2776-83 PMID: 15102684
  115. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells.
    Int J Cancer. 2008 Feb 15;122(4):761-8 PMID: 17955491
  116. Hyaluronan in morphogenesis.
    Semin Cell Dev Biol. 2001 Apr;12(2):79-87 PMID: 11292373
  117. Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells.
    J Biol Chem. 2008 May 23;283(21):14335-44 PMID: 18326857
  118. Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?
    J Cell Sci. 2008 Apr 1;121(Pt 7):925-32 PMID: 18354082
  119. The influence of hyaluronan-CD44 interaction on topoisomerase II activity and etoposide cytotoxicity in head and neck cancer.
    Arch Otolaryngol Head Neck Surg. 2007 Mar;133(3):281-8 PMID: 17372087
  120. Tumor microenvironment modulates hyaluronan expression: the lactate effect.
    J Invest Dermatol. 2006 Jun;126(6):1378-87 PMID: 16543892
  121. Hyaluronan on the surface of tumor cells is correlated with metastatic behavior.
    Cancer Res. 1995 Jan 15;55(2):428-33 PMID: 7529138
  122. Phosphatidylinositol 3'-kinase activation leads to multidrug resistance protein-1 expression and subsequent chemoresistance in advanced prostate cancer cells.
    Cancer Res. 2004 Nov 15;64(22):8397-404 PMID: 15548710
  123. Hyaluronic acid induces survival and proliferation of human myeloma cells through an interleukin-6-mediated pathway involving the phosphorylation of retinoblastoma protein.
    J Biol Chem. 2001 May 4;276(18):14728-36 PMID: 11278272
  124. EGF receptor modifies cellular responses to hyaluronan in glioblastoma cell lines.
    J Clin Neurosci. 2002 May;9(3):282-8 PMID: 12093135
  125. Induction and reversal of cell adhesion-dependent multicellular drug resistance in solid breast tumors.
    Hum Cell. 1996 Dec;9(4):257-64 PMID: 9183656
  126. CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation.
    Exp Cell Res. 2004 Apr 15;295(1):102-18 PMID: 15051494
  127. Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P-glycoprotein activity and PI3K/Akt pathway.
    Int J Cancer. 2008 Mar 1;122(5):1012-8 PMID: 17985348
  128. Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited.
    Exp Cell Res. 2002 May 15;276(1):24-31 PMID: 11978005
  129. Acid-mediated tumor invasion: a multidisciplinary study.
    Cancer Res. 2006 May 15;66(10):5216-23 PMID: 16707446
  130. CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells.
    Appl Immunohistochem Mol Morphol. 2002 Mar;10(1):34-9 PMID: 11893033
  131. ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia.
    Leukemia. 2007 Oct;21(10):2094-102 PMID: 17657220
  132. Overexpression of the receptor for hyaluronan-mediated motility (RHAMM) characterizes the malignant clone in multiple myeloma: identification of three distinct RHAMM variants.
    Blood. 1999 Mar 1;93(5):1684-96 PMID: 10029598
  133. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily.
    Cancer Res. 1995 Jan 15;55(2):434-9 PMID: 7812975
  134. Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells.
    Mol Cancer Res. 2003 Apr;1(6):420-7 PMID: 12692261
  135. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.
    Cancer Res. 1994 Mar 15;54(6):1561-5 PMID: 7511044
  136. Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2.
    J Biol Chem. 2005 May 27;280(21):20310-5 PMID: 15784621
  137. Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells.
    J Biol Chem. 2006 May 19;281(20):14026-40 PMID: 16565089
  138. Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells.
    J Biol Chem. 2006 Nov 17;281(46):34936-41 PMID: 16959784
  139. Tumorigenic potential of extracellular matrix metalloproteinase inducer.
    Am J Pathol. 2001 Jun;158(6):1921-8 PMID: 11395366
  140. Identification of pancreatic cancer stem cells.
    Cancer Res. 2007 Feb 1;67(3):1030-7 PMID: 17283135
  141. Interactions between human tumor cells and fibroblasts stimulate hyaluronate synthesis.
    Proc Natl Acad Sci U S A. 1984 Nov;81(21):6767-71 PMID: 6593727
  142. Anticancer therapeutics: a surge of new developments increasingly target tumor and stroma.
    Drug Resist Updat. 2007 Aug-Oct;10(4-5):182-93 PMID: 17855157
  143. CD133: molecule of the moment.
    J Pathol. 2008 Jan;214(1):3-9 PMID: 18067118
  144. Inhibition of tumor growth in vivo by hyaluronan oligomers.
    Int J Cancer. 1998 Jul 29;77(3):396-401 PMID: 9663602
  145. The emerging role of CD44 in regulating skeletal micrometastasis.
    Cancer Lett. 2006 Jun 8;237(1):1-9 PMID: 15979783
  146. Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study.
    Neurosurgery. 2004 Dec;55(6):1410-9; discussion 1419 PMID: 15574223
  147. Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer.
    Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):771-8 PMID: 16847188
  148. Hyaluronan-CD44 interaction with neural Wiskott-Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells.
    J Biol Chem. 2007 Jan 12;282(2):1265-80 PMID: 17092940
  149. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231.
    Cancer Res. 2007 May 1;67(9):4182-9 PMID: 17483329
  150. Interaction between CD44 and hyaluronate induces chemoresistance in non-small cell lung cancer cell.
    Cancer Lett. 2007 Jul 18;252(2):225-34 PMID: 17276588
  151. Hyaluronic acid facilitates the recovery of hematopoiesis following 5-fluorouracil administration.
    Stem Cells. 2004;22(4):544-55 PMID: 15277700
  152. Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells.
    J Biol Chem. 1997 Jan 3;272(1):24-7 PMID: 8995219
  153. Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP.
    J Biol Chem. 2007 Jul 20;282(29):20999-1004 PMID: 17540771
  154. Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells.
    Oncogene. 2006 Oct 5;25(45):6079-91 PMID: 16652145
  155. Hyaluronan metabolism: a major paradox in cancer biology.
    Pathol Biol (Paris). 2005 Sep;53(7):372-82 PMID: 16085113
  156. On the origin of cancer cells.
    Science. 1956 Feb 24;123(3191):309-14 PMID: 13298683
Article Info
Journal
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Abbr.
Drug Resist Updat
ISSN
1532-2084
DOI
10.1016/j.drup.2008.04.002
Email
toolebp@musc.edu
Published
2008-06-00
Epub
2008-00-19
Pages
110-21
Language
English
Region
Scotland
NLM ID
9815369
PMCID
PMC2584579
Subset
IM
Grants
NCI NIH HHS · R01 CA073839 · United States
NCI NIH HHS · R01 CA082867-08 · United States
NCI NIH HHS · CA082867 · United States
NCI NIH HHS · R01 CA073839-10 · United States
NCI NIH HHS · R01 CA082867 · United States
NCI NIH HHS · CA073839 · United States
External Links
PubMed source DOI: 10.1016/j.drup.2008.04.002 PMC Full Text View journal details
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