Mostrar el registro sencillo del ítem
dc.contributor.author
Lompardía, Silvina Laura
dc.contributor.author
Papademetrio, Daniela Laura
dc.contributor.author
Mascaró, Marilina
dc.contributor.author
Alvarez Carbonetto, Elida M. del C.
dc.contributor.author
Hajos, Silvia Elvira
dc.date.available
2016-11-08T18:41:36Z
dc.date.issued
2013-11
dc.identifier.citation
Lompardía, Silvina Laura; Papademetrio, Daniela Laura; Mascaró, Marilina; Alvarez Carbonetto, Elida M. del C.; Hajos, Silvia Elvira; Human leukaemic cell lines synthesize hyaluronan to avoid senescence and resist chemotherapy; Oxford Univ Press Inc; Glycobiology; 23; 12; 11-2013; 1463-1476
dc.identifier.issn
0959-6658
dc.identifier.uri
http://hdl.handle.net/11336/8056
dc.description.abstract
Hyaluronan (HA) is one of the major components of the extracellular matrix. Several solid tumors produce high levels of HA, which promotes survival and multidrug resistance (MDR). HA oligomers (oHAs) can block HA effects. However, little is known about the role of HA in hematological malignancies. The aim of this work was to determine whether HA or its oligomers can modulate the proliferation of leukemia cells as well as their effect on MDR. Receptors and signaling pathways involved were also analyzed. For this purpose, the human leukemic cell lines K562 and Kv562, which are sensitive and resistant to Vincristine (VCR), respectively, were used. We demonstrated that HA induced cell proliferation in both cell lines. On K562 cells, this effect was mediated by cluster differentiation 44 (CD44) and activation of both phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, whereas on Kv562 cells, the effect was mediated by receptor for hyaluronan-mediated motility (RHAMM) and PI3K/Akt activation. The inhibition of HA synthesis by 4-methylumbelliferone (4MU) decreased cell line proliferation and sensitized Kv562 to the effect of VCR through P-glycoprotein (Pgp) inhibition, in both cases with senescence induction. Moreover, oHAs inhibited K562 proliferation mediated by CD44 as well as Akt and ERK down-regulation. Furthermore, oHAs sensitized Kv562 cells to VCR by Pgp inhibition inducing senescence. We postulate that the synthesis of HA would promote leukemia progression mediated by the triggering of the above-mentioned proliferative signals. These findings highlight the potential use of oHAs and 4MU as coadjuvant for drug-resistant leukemia.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford Univ Press Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hyaluronan
dc.subject
Cd44 / Rhamm
dc.subject
Senescence
dc.subject
Drug-Resistance
dc.subject
Leukaemia
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Human leukaemic cell lines synthesize hyaluronan to avoid senescence and resist chemotherapy
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-11-07T15:40:50Z
dc.journal.volume
23
dc.journal.number
12
dc.journal.pagination
1463-1476
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.conicet.avisoEditorial
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Glycobiology following peer review. The version of record Glycobiology (2013) 23 (12): 1463-1476 is available online at: doi: 10.1093/glycob/cwt074
dc.description.fil
Fil: Lompardía, Silvina Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
dc.description.fil
Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
dc.description.fil
Fil: Mascaró, Marilina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
dc.description.fil
Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
dc.description.fil
Fil: Hajos, Silvia Elvira. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina
dc.journal.title
Glycobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://glycob.oxfordjournals.org/content/23/12/1463.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1093/glycob/cwt074
Archivos asociados