The main findings of this thesis are:
Active hyaluronan synthesis relocates filamentous actin to the cell cortex and apical filopodia, thus regulating plasma membrane and actin dynamics
A thick hyaluronan coat acts like an extracellular cytoskeleton in order to maintain the long and dynamic apical filopodia with only approximately 8 actin filaments
Hyaluronan production is required for, and supported by, the apical filopodia Mesothelial plasma membrane protrusions and the HAS-‐‑induced plasma membrane protrusions are ultrastructurally similar, suggesting that the hyaluronan-‐‑positive protrusions in the mesothelium represent apical filopodia in vivo
Hyaluronan synthesis is associated with microvesicle formation and the HAS-‐‑
induced apical filopodia act as a platform for the budding of the hyaluronan coated microvesicles
EMT is associated with the activation of the hyaluronan synthesis machinery, apical filopodia and microvesicle formation
In the future, the role of the actin binding proteins in the formation of the HAS-‐‑induced apical filopodia should be studied in more detail. Increased hyaluronan production and actin binding proteins such as ezrin and fascin are associated with cancer progression. It is possible that the HAS-‐‑induced apical filopodia have a role in cancer invasion and metastasis. Thus, their detailed investigation may reveal new targets for cancer treatment.
Myo10 was shown to specifically localize on the tips of the HAS-‐‑induced apical filopodia, but it is not required for their formation. Myo10 may function as a cargo carrier, and be involved in the formation of the bulbous expansion (Rilla and Koistinen 2015) at the tip. Therefore, Myo10 may have a role in microvesicle formation.
In this thesis, it was shown that normal mesothelium in vivo is positive for hyaluronan and all of its synthases, but negative for CD44. We do not, however, know if the mesothelial cell protrusions are dependent on hyaluronan-‐‑like HAS-‐‑induced protrusions. Knockout animals would be potential tools to investigate the role of the different HASes in the filopodia in vivo.
8 References
Abraham S, Scarcia M, Bagshaw RD, McMahon K, Grant G, Harvey T, Yeo M, Esteves FO, Thygesen HH, Jones PF, Speirs V, Hanby AM, Selby PJ, Lorger M, Dear TN, Pawson T, Marshall CJ, Mavria G (2015) A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. Nat Commun 6:7286.
Acharya S, Rodriguez IR, Moreira EF, Midura RJ, Misono K, Todres E, Hollyfield JG (1998) SPACR, a novel interphotoreceptor matrix glycoprotein in human retina that interacts with hyaluronan. J Biol Chem 273:31599-‐‑31606.
Adachi T, Arito M, Suematsu N, Kamijo-‐‑Ikemori A, Omoteyama K, Sato T, Kurokawa MS, Okamoto K, Kimura K, Shibagaki Y, Kato T (2015) Roles of layilin in TNF-‐‑alpha-‐‑induced epithelial-‐‑mesenchymal transformation of renal tubular epithelial cells. Biochem Biophys Res Commun.
Adamia S, Crainie M, Kriangkum J, Mant MJ, Belch AR, Pilarski LM (2003) Abnormal expression of hyaluronan synthases in patients with Waldenstrom'ʹs macroglobulimenia. Semin Oncol 30:165-‐‑168.
Adamia S, Kriangkum J, Belch AR, Pilarski LM (2014) Aberrant posttranscriptional processing of hyaluronan synthase 1 in malignant transformation and tumor progression. Adv Cancer Res 123:67-‐‑94.
Adamia S, Reiman T, Crainie M, Mant MJ, Belch AR, Pilarski LM (2005a) Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma. Blood 105:4836-‐‑4844.
Adamia S, Treon SP, Reiman T, Tournilhac O, McQuarrie C, Mant MJ, Belch AR, Pilarski LM (2005b) Potential impact of a single nucleotide polymorphism in the hyaluronan synthase 1 gene in Waldenstrom'ʹs macroglobulinemia. Clin Lymphoma 5:253-‐‑256.
Adams JC (1997) Characterization of cell-‐‑matrix adhesion requirements for the formation of fascin microspikes. Mol Biol Cell 8:2345-‐‑2363.
Adams JC, Schwartz MA (2000) Stimulation of fascin spikes by thrombospondin-‐‑1 is mediated by the GTPases Rac and Cdc42. J Cell Biol 150:807-‐‑822.
Adamson IY, Bakowska J, Prieditis H (2000) Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors. Am J Respir Cell Mol Biol 23:345-‐‑349.
Afify AM, Stern R, Michael CW (2005) Differentiation of mesothelioma from adenocarcinoma in serous effusions: the role of hyaluronic acid and CD44 localization. Diagn Cytopathol 32:145-‐‑150.
Ågren UM, Tammi RH, Tammi MI (1997) Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Radic Biol Med 23:996-‐‑1001.
principal mediator of hyaluronic-‐‑acid-‐‑induced melanoma cell proliferation. J Invest Dermatol 116:93-‐‑
101.
Aitken K, Bagl DJ (2001) Stretch-‐‑induced bladder smooth muscle cell (SMC) proliferation is mediated by RHAMM-‐‑dependent extracellular-‐‑regulated kinase (erk) signaling. Urology 57:109.
Akiyama Y, Jung S, Salhia B, Lee S, Hubbard S, Taylor M, Mainprize T, Akaishi K, van Furth W, Rutka JT (2001) Hyaluronate receptors mediating glioma cell migration and proliferation. J Neurooncol 53:115-‐‑
127.
Albeiroti S, Ayasoufi K, Hill DR, Shen B, de la Motte CA (2015) Platelet hyaluronidase-‐‑2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation. Blood 125:1460-‐‑1469.
Albertine KH, Wiener-‐‑Kronish JP, Roos PJ, Staub NC (1982) Structure, blood supply, and lymphatic vessels of the sheep'ʹs visceral pleura. Am J Anat 165:277-‐‑294.
Albrecht-‐‑Buehler G (1976) Filopodia of spreading 3T3 cells. Do they have a substrate-‐‑exploring function?. J Cell Biol 69:275-‐‑286.
Algrain M, Turunen O, Vaheri A, Louvard D, Arpin M (1993) Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-‐‑cytoskeletal linker. J Cell Biol 120:129-‐‑139.
Alho AM, Underhill CB (1989) The hyaluronate receptor is preferentially expressed on proliferating epithelial cells. J Cell Biol 108:1557-‐‑1565.
Ali G, Borrelli N, Riccardo G, Proietti A, Pelliccioni S, Niccoli C, Boldrini L, Lucchi M, Mussi A, Fontanini G (2013) Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia. J Thorac Oncol 8:1389-‐‑
1395.
Andre B, Duterme C, Van Moer K, Mertens-‐‑Strijthagen J, Jadot M, Flamion B (2011) Hyal2 is a glycosylphosphatidylinositol-‐‑anchored, lipid raft-‐‑associated hyaluronidase. Biochem Biophys Res Commun 411:175-‐‑179.
Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L (2002) Malignant effusions and immunogenic tumour-‐‑derived exosomes. Lancet 360:295-‐‑305.
Anttila MA, Tammi RH, Tammi MI, Syrjänen KJ, Saarikoski SV, Kosma VM (2000) High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res 60:150-‐‑155.
Arboleda-‐‑Estudillo Y, Krieg M, Stuhmer J, Licata NA, Muller DJ, Heisenberg CP (2010) Movement directionality in collective migration of germ layer progenitors. Curr Biol 20:161-‐‑169.
Arjonen A, Kaukonen R, Ivaska J (2011) Filopodia and adhesion in cancer cell motility. Cell Adh Migr 5:421-‐‑430.
Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H, Ivaska J (2014) Mutant p53-‐‑associated myosin-‐‑X upregulation promotes breast cancer invasion and metastasis. J Clin Invest 124:1069-‐‑1082.
Arnoux V, Nassour M, L'ʹHelgoualc'ʹh A, Hipskind RA, Savagner P (2008) Erk5 controls Slug expression and keratinocyte activation during wound healing. Mol Biol Cell 19:4738-‐‑4749.
Arranz AM, Perkins KL, Irie F, Lewis DP, Hrabe J, Xiao F, Itano N, Kimata K, Hrabetova S, Yamaguchi Y (2014) Hyaluronan deficiency due to Has3 knock-‐‑out causes altered neuronal activity and seizures via reduction in brain extracellular space. J Neurosci 34:6164-‐‑6176.
Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303-‐‑1313.
Asea A, Jean-‐‑Pierre C, Kaur P, Rao P, Linhares IM, Skupski D, Witkin SS (2008) Heat shock protein-‐‑
containing exosomes in mid-‐‑trimester amniotic fluids. J Reprod Immunol 79:12-‐‑17.
Aso T, Matsuo M, Kiyohara H, Taguchi K, Rikimaru F, Shimokawa M, Segawa Y, Higaki Y, Umeno H, Nakashima T, Masuda M (2015) Induction of CD44 variant 9-‐‑expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer. PLoS One 10:e0116596.
Asplund T, Brinck J, Suzuki M, Briskin MJ, Heldin P (1998) Characterization of hyaluronan synthase from a human glioma cell line. Biochim Biophys Acta 1380:377-‐‑388.
Asplund T, Heldin P (1994) Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. Cancer Res 54:4516-‐‑4523.
Asplund T, Versnel MA, Laurent TC, Heldin P (1993) Human mesothelioma cells produce factors that stimulate the production of hyaluronan by mesothelial cells and fibroblasts. Cancer Res 53:388-‐‑392.
Assmann V, Jenkinson D, Marshall JF, Hart IR (1999) The intracellular hyaluronan receptor RHAMM/IHABP interacts with microtubules and actin filaments. J Cell Sci 112 ( Pt 22):3943-‐‑3954.
Atmuri V, Martin DC, Hemming R, Gutsol A, Byers S, Sahebjam S, Thliveris JA, Mort JS, Carmona E, Anderson JE, Dakshinamurti S, Triggs-‐‑Raine B (2008) Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation. Matrix Biol 27:653-‐‑660.
Augustin F, Fiegl M, Schmid T, Pomme G, Sterlacci W, Tzankov A (2015) Receptor for hyaluronic acid-‐‑
mediated motility (RHAMM, CD168) expression is prognostically important in both nodal negative and nodal positive large cell lung cancer. J Clin Pathol 68:368-‐‑373.
Auvinen P, Rilla K, Tumelius R, Tammi M, Sironen R, Soini Y, Kosma VM, Mannermaa A, Viikari J, Tammi R (2014) Hyaluronan synthases (HAS1-‐‑3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival. Breast Cancer Res Treat 143:277-‐‑286.
Auvinen P, Tammi R, Kosma VM, Sironen R, Soini Y, Mannermaa A, Tumelius R, Uljas E, Tammi M (2013) Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer. Int J Cancer 132:531-‐‑539.
Regen 22:579-‐‑593.
Baggenstoss BA, Weigel PH (2006) Size exclusion chromatography-‐‑multiangle laser light scattering analysis of hyaluronan size distributions made by membrane-‐‑bound hyaluronan synthase. Anal Biochem 352:243-‐‑251.
Bai KJ, Spicer AP, Mascarenhas MM, Yu L, Ochoa CD, Garg HG, Quinn DA (2005) The role of hyaluronan synthase 3 in ventilator-‐‑induced lung injury. Am J Respir Crit Care Med 172:92-‐‑98.
Bai Y, Wu B, Terada N, Ohno N, Saitoh S, Saitoh Y, Ohno S (2011) Histological study and LYVE-‐‑1 immunolocalization of mouse mesenteric lymph nodes with "ʺIn Vivo Cryotechnique"ʺ. Acta Histochem Cytochem 44:81-‐‑90.
Bainbridge P (2013) Wound healing and the role of fibroblasts. J Wound Care 22:407-‐‑8, 410-‐‑12.
Bajorath J, Greenfield B, Munro SB, Day AJ, Aruffo A (1998) Identification of CD44 residues important for hyaluronan binding and delineation of the binding site. J Biol Chem 273:338-‐‑343.
Baker PM, Clement PB, Young RH (2014) Selected topics in peritoneal pathology. Int J Gynecol Pathol 33:393-‐‑401.
Bakhti M, Winter C, Simons M (2011) Inhibition of myelin membrane sheath formation by oligodendrocyte-‐‑derived exosome-‐‑like vesicles. J Biol Chem 286:787-‐‑796.
Bakkers J, Kramer C, Pothof J, Quaedvlieg NE, Spaink HP, Hammerschmidt M (2004) Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells during zebrafish gastrulation. Development 131:525-‐‑537.
Balazs EA, Laurent TC, Jeanloz RW (1986) Nomenclature of hyaluronic acid. Biochem J 235:903.
Banerji S, Day AJ, Kahmann JD, Jackson DG (1998) Characterization of a functional hyaluronan-‐‑binding domain from the human CD44 molecule expressed in Escherichia coli. Protein Expr Purif 14:371-‐‑381.
Banerji S, Hide BR, James JR, Noble ME, Jackson DG (2010) Distinctive properties of the hyaluronan-‐‑
binding domain in the lymphatic endothelial receptor Lyve-‐‑1 and their implications for receptor function. J Biol Chem 285:10724-‐‑10735.
Banerji S, Lawrance W, Metcalfe C, Briggs DC, Yamauchi A, Dushek O, van der Merwe PA, Day AJ, Jackson DG (2016) Homodimerization of the Lymph Vessel Endothelial Receptor LYVE-‐‑1 through a Redox-‐‑labile Disulfide Is Critical for Hyaluronan Binding in Lymphatic Endothelium. J Biol Chem 291:25004-‐‑25018.
Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG (1999) LYVE-‐‑1, a new homologue of the CD44 glycoprotein, is a lymph-‐‑specific receptor for hyaluronan. J Cell Biol 144:789-‐‑
801.
Cd44-‐‑hyaluronan complex provide insight into a fundamental carbohydrate-‐‑protein interaction. Nat Struct Mol Biol 14:234-‐‑239.
Banner DW, Bloomer AC, Petsko GA, Phillips DC, Pogson CI, Wilson IA, Corran PH, Furth AJ, Milman JD, Offord RE, Priddle JD, Waley SG (1975) Structure of chicken muscle triose phosphate isomerase determined crystallographically at 2.5 angstrom resolution using amino acid sequence data. Nature 255:609-‐‑614.
Bao W, Fu HJ, Xie QS, Wang L, Zhang R, Guo ZY, Zhao J, Meng YL, Ren XL, Wang T, Li Q, Jin BQ, Yao LB, Wang RA, Fan DM, Chen SY, Jia LT, Yang AG (2011) HER2 interacts with CD44 to up-‐‑regulate CXCR4 via epigenetic silencing of microRNA-‐‑139 in gastric cancer cells. Gastroenterology 141:2076-‐‑
2087.e6.
Barbul A, Knud-‐‑Hansen J, Wasserkrug HL, Efron G (1986) Interleukin 2 enhances wound healing in rats.
J Surg Res 40:315-‐‑319.
Bard JB, McBride WH, Ross AR (1983) Morphology of hyaluronidase-‐‑sensitive cell coats as seen in the SEM after freeze-‐‑drying. J Cell Sci 62:371-‐‑383.
Barry DM, Xu K, Meadows SM, Zheng Y, Norden PR, Davis GE, Cleaver O (2015) Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation in mice. Development 142:3058-‐‑3070.
Bart G, Vico NO, Hassinen A, Pujol FM, Deen AJ, Ruusala A, Tammi RH, Squire A, Heldin P, Kellokumpu S, Tammi MI (2015) Fluorescence Resonance Energy Transfer (FRET) and Proximity Ligation Assays Reveal Functionally Relevant Homo-‐‑ and Heteromeric Complexes among Hyaluronan Synthases HAS1, HAS2, and HAS3. J Biol Chem 290:11479-‐‑11490.
Bayliss MT, Howat SL, Dudhia J, Murphy JM, Barry FP, Edwards JC, Day AJ (2001) Up-‐‑regulation and differential expression of the hyaluronan-‐‑binding protein TSG-‐‑6 in cartilage and synovium in rheumatoid arthritis and osteoarthritis. Osteoarthritis Cartilage 9:42-‐‑48.
Bennett KL, Jackson DG, Simon JC, Tanczos E, Peach R, Modrell B, Stamenkovic I, Plowman G, Aruffo A (1995) CD44 isoforms containing exon V3 are responsible for the presentation of heparin-‐‑binding growth factor. J Cell Biol 128:687-‐‑698.
Berg JS, Cheney RE (2002) Myosin-‐‑X is an unconventional myosin that undergoes intrafilopodial motility. Nat Cell Biol 4:246-‐‑250.
Berg JS, Derfler BH, Pennisi CM, Corey DP, Cheney RE (2000) Myosin-‐‑X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin. J Cell Sci 113 Pt 19:3439-‐‑3451.
Bermudez E, Everitt J, Walker C (1990) Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture. Exp Cell Res 190:91-‐‑98.
Bernert B, Porsch H, Heldin P (2011) Hyaluronan synthase 2 (HAS2) promotes breast cancer cell invasion by suppression of tissue metalloproteinase inhibitor 1 (TIMP-‐‑1). J Biol Chem 286:42349-‐‑42359.
filament buckling and the production of forces. Biophys J 92:2546-‐‑2558.
Berryman M, Franck Z, Bretscher A (1993) Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J Cell Sci 105 ( Pt 4):1025-‐‑1043.
Bianchi F, Sala E, Donadei C, Capelli I, La Manna G (2014) Potential advantages of acute kidney injury management by mesenchymal stem cells. World J Stem Cells 6:644-‐‑650.
Bianco F, Perrotta C, Novellino L, Francolini M, Riganti L, Menna E, Saglietti L, Schuchman EH, Furlan R, Clementi E, Matteoli M, Verderio C (2009) Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28:1043-‐‑1054.
Bird SD, Hasan Q, Davis PF, Walker RJ (1998) Platelet derived growth factor-‐‑BB induced calcium transients in cultured human peritoneal mesothelial cells. ASAIO J 44:835-‐‑840.
Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168:3235-‐‑3241.
Blom AM, Morgelin M, Oyen M, Jarvet J, Fries E (1999) Structural characterization of inter-‐‑alpha-‐‑
inhibitor. Evidence for an extended shape. J Biol Chem 274:298-‐‑304.
Blundell CD, Mahoney DJ, Almond A, DeAngelis PL, Kahmann JD, Teriete P, Pickford AR, Campbell ID, Day AJ (2003) The link module from ovulation-‐‑ and inflammation-‐‑associated protein TSG-‐‑6 changes conformation on hyaluronan binding. J Biol Chem 278:49261-‐‑49270.
Bobrie A, Colombo M, Raposo G, Thery C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12:1659-‐‑1668.
Bodega F, Sironi C, Porta C, Pecchiari M, Zocchi L, Agostoni E (2013) Mixed lubrication after rewetting of blotted pleural mesothelium. Respir Physiol Neurobiol 185:369-‐‑373.
Bodevin-‐‑Authelet S, Kusche-‐‑Gullberg M, Pummill PE, DeAngelis PL, Lindahl U (2005) Biosynthesis of hyaluronan: direction of chain elongation. J Biol Chem 280:8813-‐‑8818.
Bohil AB, Robertson BW, Cheney RE (2006) Myosin-‐‑X is a molecular motor that functions in filopodia formation. Proc Natl Acad Sci U S A 103:12411-‐‑12416.
Bohrer LR, Chuntova P, Bade LK, Beadnell TC, Leon RP, Brady NJ, Ryu Y, Goldberg JE, Schmechel SC, Koopmeiners JS, McCarthy JB, Schwertfeger KL (2014) Activation of the FGFR-‐‑STAT3 pathway in breast cancer cells induces a hyaluronan-‐‑rich microenvironment that licenses tumor formation. Cancer Res 74:374-‐‑386.
Bollyky PL, Falk BA, Wu RP, Buckner JH, Wight TN, Nepom GT (2009) Intact extracellular matrix and the maintenance of immune tolerance: high molecular weight hyaluronan promotes persistence of induced CD4+CD25+ regulatory T cells. J Leukoc Biol 86:567-‐‑572.
antibodies recognizing the N-‐‑ and C-‐‑terminal regions of talin disrupt actin stress fibers when microinjected into human fibroblasts. Cell Motil Cytoskeleton 36:363-‐‑376.
Bonilha VL, Finnemann SC, Rodriguez-‐‑Boulan E (1999) Ezrin promotes morphogenesis of apical microvilli and basal infoldings in retinal pigment epithelium. J Cell Biol 147:1533-‐‑1548.
Bono P, Rubin K, Higgins JM, Hynes RO (2001) Layilin, a novel integral membrane protein, is a hyaluronan receptor. Mol Biol Cell 12:891-‐‑900.
Bordeleau F, Chan B, Antonyak MA, Lampi MC, Cerione RA, Reinhart-‐‑King CA (2015) Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility. J Biomech.
Bornschlögl T (2013) How filopodia pull: what we know about the mechanics and dynamics of filopodia.
Cytoskeleton (Hoboken) 70:590-‐‑603.
Borowsky ML, Hynes RO (1998) Layilin, a novel talin-‐‑binding transmembrane protein homologous with C-‐‑type lectins, is localized in membrane ruffles. J Cell Biol 143:429-‐‑442.
Bost F, Diarra-‐‑Mehrpour M, Martin JP (1998) Inter-‐‑alpha-‐‑trypsin inhibitor proteoglycan family-‐‑-‐‑a group of proteins binding and stabilizing the extracellular matrix. Eur J Biochem 252:339-‐‑346.
Boureux A, Vignal E, Faure S, Fort P (2007) Evolution of the Rho family of ras-‐‑like GTPases in eukaryotes. Mol Biol Evol 24:203-‐‑216.
Bourguignon LY, Gilad E, Peyrollier K (2007) Heregulin-‐‑mediated ErbB2-‐‑ERK signaling activates hyaluronan synthases leading to CD44-‐‑dependent ovarian tumor cell growth and migration. J Biol Chem 282:19426-‐‑19441.
Bourguignon LY, Gilad E, Rothman K, Peyrollier K (2005) Hyaluronan-‐‑CD44 interaction with IQGAP1 promotes Cdc42 and ERK signaling, leading to actin binding, Elk-‐‑1/estrogen receptor transcriptional activation, and ovarian cancer progression. J Biol Chem 280:11961-‐‑11972.
Bourguignon LY, Zhu H, Chu A, Iida N, Zhang L, Hung MC (1997) Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation. J Biol Chem 272:27913-‐‑27918.
Bourguignon LY, Zhu H, Shao L, Chen YW (2001) CD44 interaction with c-‐‑Src kinase promotes cortactin-‐‑mediated cytoskeleton function and hyaluronic acid-‐‑dependent ovarian tumor cell migration. J Biol Chem 276:7327-‐‑7336.
Bourguignon LY, Zhu H, Shao L, Chen YW (2000) CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-‐‑mediated breast tumor cell migration. J Biol Chem 275:1829-‐‑1838.
Brauner A, Hylander B, Wretlind B (1993) Interleukin-‐‑6 and interleukin-‐‑8 in dialysate and serum from patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 22:430-‐‑435.
Synthesis of hyaluronic acid by human peritoneal mesothelial cells: effect of cytokines and dialysate.
Perit Dial Int 16:374-‐‑378.
Breborowicz A, Wisniewska J, Polubinska A, Wieczorowska-‐‑Tobis K, Martis L, Oreopoulos DG (1998) Role of peritoneal mesothelial cells and fibroblasts in the synthesis of hyaluronan during peritoneal dialysis. Perit Dial Int 18:382-‐‑386.
Bretscher A (1989) Rapid phosphorylation and reorganization of ezrin and spectrin accompany morphological changes induced in A-‐‑431 cells by epidermal growth factor. J Cell Biol 108:921-‐‑930.
Bretscher MS, Aguado-‐‑Velasco C (1998) EGF induces recycling membrane to form ruffles. Curr Biol 8:721-‐‑724.
Brinck J, Heldin P (1999) Expression of recombinant hyaluronan synthase (HAS) isoforms in CHO cells reduces cell migration and cell surface CD44. Exp Cell Res 252:342-‐‑351.
Bros M, Ross XL, Pautz A, Reske-‐‑Kunz AB, Ross R (2003) The human fascin gene promoter is highly active in mature dendritic cells due to a stage-‐‑specific enhancer. J Immunol 171:1825-‐‑1834.
Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, Morando L, Busca A, Falda M, Bussolati B, Tetta C, Camussi G (2009) Mesenchymal stem cell-‐‑derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 20:1053-‐‑1067.
Bryan J, Edwards R, Matsudaira P, Otto J, Wulfkuhle J (1993) Fascin, an echinoid actin-‐‑bundling protein, is a homolog of the Drosophila singed gene product. Proc Natl Acad Sci U S A 90:9115-‐‑9119.
Bullard KM, Kim HR, Wheeler MA, Wilson CM, Neudauer CL, Simpson MA, McCarthy JB (2003) Hyaluronan synthase-‐‑3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth. Int J Cancer 107:739-‐‑746.
Caby MP, Lankar D, Vincendeau-‐‑Scherrer C, Raposo G, Bonnerot C (2005) Exosomal-‐‑like vesicles are present in human blood plasma. Int Immunol 17:879-‐‑887.
Cai JL, Li M, Na YQ (2011) Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma. Chin J Cancer Res 23:59-‐‑63.
Camenisch TD, Spicer AP, Brehm-‐‑Gibson T, Biesterfeldt J, Augustine ML, Calabro A,Jr, Kubalak S, Klewer SE, McDonald JA (2000) Disruption of hyaluronan synthase-‐‑2 abrogates normal cardiac morphogenesis and hyaluronan-‐‑mediated transformation of epithelium to mesenchyme. J Clin Invest 106:349-‐‑360.
Cannistra SA, Ottensmeier C, Tidy J, DeFranzo B (1994) Vascular cell adhesion molecule-‐‑1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. Exp Hematol 22:996-‐‑1002.
Cant K, Cooley L (1996) Single amino acid mutations in Drosophila fascin disrupt actin bundling function in vivo. Genetics 143:249-‐‑258.
cancer patients. J Surg Oncol 110:727-‐‑733.
Carugo O, Cemazar M, Zahariev S, Hudaky I, Gaspari Z, Perczel A, Pongor S (2003) Vicinal disulfide turns. Protein Eng 16:637-‐‑639.
Casini P, Nardi I, Ori M (2012) Hyaluronan is required for cranial neural crest cells migration and craniofacial development. Dev Dyn 241:294-‐‑302.
Castor CW, Greene JA (1968) Regional distribution of acid mucopolysaccharides in the kidney. J Clin Invest 47:2125-‐‑2132.
Chang IW, Liang PI, Li CC, Wu WJ, Huang CN, Lin VC, Hsu CT, He HL, Wu TF, Hung CH, Li CF (2015) HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder. Tumour Biol 36:5441-‐‑5450.
Chang MY, Tanino Y, Vidova V, Kinsella MG, Chan CK, Johnson PY, Wight TN, Frevert CW (2014) Reprint of: A rapid increase in macrophage-‐‑derived versican and hyaluronan in infectious lung disease.
Matrix Biol 35:162-‐‑173.
Chao H, Spicer AP (2005) Natural antisense mRNAs to hyaluronan synthase 2 inhibit hyaluronan biosynthesis and cell proliferation. J Biol Chem 280:27513-‐‑27522.
Chao KL, Muthukumar L, Herzberg O (2007) Structure of human hyaluronidase-‐‑1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. Biochemistry 46:6911-‐‑6920.
Chapple IL (1997) Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 24:287-‐‑296.
Chen KS, Chen WS (2012) Experience in primary culture of human peritoneal mesothelial cell. Chin J
Chen KS, Chen WS (2012) Experience in primary culture of human peritoneal mesothelial cell. Chin J