• Je něco špatně v tomto záznamu ?

CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma

S. Thangavadivel, C. Zelle-Rieser, A. Olivier, B. Postert, G. Untergasser, J. Kern, A. Brunner, E. Gunsilius, R. Biedermann, R. Hajek, L. Pour, W. Willenbacher, R. Greil, K. Jöhrer,

. 2016 ; 7 (48) : 78605-78618.

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18010995

The bone marrow microenvironment plays a decisive role in multiple myeloma progression and drug resistance. Chemokines are soluble mediators of cell migration, proliferation and survival and essentially modulate tumor progression and drug resistance. Here we investigated bone marrow-derived chemokines of naive and therapy-refractory myeloma patients and discovered that high levels of the chemokine CCL27, known so far for its role in skin inflammatory processes, correlated with worse overall survival of the patients. In addition, chemokine levels were significantly higher in samples from patients who became refractory to bortezomib at first line treatment compared to resistance at later treatment lines.In vitro as well as in an in vivo model we could show that CCL27 triggers bortezomib-resistance of myeloma cells. This effect was strictly dependent on the expression of the respective receptor, CCR10, on stroma cells and involved the modulation of IL-10 expression, activation of myeloma survival pathways, and modulation of proteasomal activity. Drug resistance could be totally reversed by blocking CCR10 by siRNA as well as blocking IL-10 and its receptor.From our data we suggest that blocking the CCR10/CCL27/IL-10 myeloma-stroma crosstalk is a novel therapeutic target that could be especially relevant in early refractory myeloma patients.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18010995
003      
CZ-PrNML
005      
20180404142448.0
007      
ta
008      
180404s2016 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.18632/oncotarget.12522 $2 doi
035    __
$a (PubMed)27732933
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Thangavadivel, Shanmugapriya $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
245    10
$a CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma / $c S. Thangavadivel, C. Zelle-Rieser, A. Olivier, B. Postert, G. Untergasser, J. Kern, A. Brunner, E. Gunsilius, R. Biedermann, R. Hajek, L. Pour, W. Willenbacher, R. Greil, K. Jöhrer,
520    9_
$a The bone marrow microenvironment plays a decisive role in multiple myeloma progression and drug resistance. Chemokines are soluble mediators of cell migration, proliferation and survival and essentially modulate tumor progression and drug resistance. Here we investigated bone marrow-derived chemokines of naive and therapy-refractory myeloma patients and discovered that high levels of the chemokine CCL27, known so far for its role in skin inflammatory processes, correlated with worse overall survival of the patients. In addition, chemokine levels were significantly higher in samples from patients who became refractory to bortezomib at first line treatment compared to resistance at later treatment lines.In vitro as well as in an in vivo model we could show that CCL27 triggers bortezomib-resistance of myeloma cells. This effect was strictly dependent on the expression of the respective receptor, CCR10, on stroma cells and involved the modulation of IL-10 expression, activation of myeloma survival pathways, and modulation of proteasomal activity. Drug resistance could be totally reversed by blocking CCR10 by siRNA as well as blocking IL-10 and its receptor.From our data we suggest that blocking the CCR10/CCL27/IL-10 myeloma-stroma crosstalk is a novel therapeutic target that could be especially relevant in early refractory myeloma patients.
650    _2
$a senioři $7 D000368
650    _2
$a apoptóza $x účinky léků $7 D017209
650    _2
$a bortezomib $x farmakologie $7 D000069286
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a pohyb buněk $x účinky léků $7 D002465
650    _2
$a proliferace buněk $x účinky léků $7 D049109
650    _2
$a chemokin CCL27 $x metabolismus $7 D054425
650    12
$a chemorezistence $7 D019008
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a interleukin-10 $x genetika $x metabolismus $7 D016753
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mnohočetný myelom $x farmakoterapie $x enzymologie $x genetika $x patologie $7 D009101
650    _2
$a proteasomový endopeptidasový komplex $x metabolismus $7 D046988
650    _2
$a inhibitory proteasomu $x farmakologie $7 D061988
650    _2
$a RNA interference $7 D034622
650    _2
$a interakce mezi receptory a ligandy $x účinky léků $7 D020239
650    _2
$a receptory CCR10 $x genetika $x metabolismus $7 D054447
650    _2
$a receptory interleukinu-10 $x genetika $x metabolismus $7 D053701
650    _2
$a signální transdukce $x účinky léků $7 D015398
650    _2
$a transfekce $7 D014162
650    _2
$a nádorové mikroprostředí $7 D059016
650    _2
$a xenogenní modely - testy antitumorózní aktivity $7 D023041
655    _2
$a časopisecké články $7 D016428
700    1_
$a Zelle-Rieser, Claudia $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
700    1_
$a Olivier, Angelika $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
700    1_
$a Postert, Benno $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
700    1_
$a Untergasser, Gerold $u Tyrolean Cancer Research Institute, Innsbruck, Austria. Laboratory of Tumor Angiogenesis and Tumorbiology, Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
700    1_
$a Kern, Johann $u Laboratory of Tumor Angiogenesis and Tumorbiology, Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
700    1_
$a Brunner, Andrea $u Department of Pathology, Medical University Innsbruck, Innsbruck, Austria.
700    1_
$a Gunsilius, Eberhard $u Laboratory of Tumor Angiogenesis and Tumorbiology, Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
700    1_
$a Biedermann, Rainer $u Department of Orthopedic Surgery, Medical University Innsbruck, Innsbruck, Austria.
700    1_
$a Hajek, Roman $u Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Department of Clinical Hematology, University Hospital Brno, Brno, Czech Republic. Department of Hematooncology, Faculty of Medicine, University of Ostrava and University Hospital Ostrava, Ostrava, Czech Republic.
700    1_
$a Pour, Ludek $u Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Department of Clinical Hematology, University Hospital Brno, Brno, Czech Republic. Department of Hematooncology, Faculty of Medicine, University of Ostrava and University Hospital Ostrava, Ostrava, Czech Republic.
700    1_
$a Willenbacher, Wolfgang $u Department of Internal Medicine V, University Hospital Innsbruck, Innsbruck, Austria.
700    1_
$a Greil, Richard $u Tyrolean Cancer Research Institute, Innsbruck, Austria. Salzburg Cancer Research Institute-Laboratory of Immunological and Molecular Cancer Research, Salzburg, Austria. Third Medical Department at The Paracelsus Medical University Salzburg, Austria. Cancer Cluster Salzburg (CCS), Salzburg, Austria.
700    1_
$a Jöhrer, Karin $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
773    0_
$w MED00184852 $t Oncotarget $x 1949-2553 $g Roč. 7, č. 48 (2016), s. 78605-78618
856    41
$u https://pubmed.ncbi.nlm.nih.gov/27732933 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180404 $b ABA008
991    __
$a 20180404142527 $b ABA008
999    __
$a ok $b bmc $g 1288480 $s 1007807
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 7 $c 48 $d 78605-78618 $i 1949-2553 $m Oncotarget $n Oncotarget $x MED00184852
LZP    __
$a Pubmed-20180404

Najít záznam

Citační ukazatele

Možnosti archivace