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Naslov:Cathepsin K cleavage of SDF-1[alpha] inhibits its chemotactic activity towards glioblastoma stem-like cells
Avtorji:ID Hira, Vashendriya V. V. (Avtor)
ID Verbovšek, Urška (Avtor)
ID Breznik, Barbara (Avtor)
ID Srdič, Matic (Avtor)
ID Novinec, Marko (Avtor)
ID Kakar, Hala (Avtor)
ID Wormer, Jill (Avtor)
ID Swaan, Britt van der (Avtor)
ID Lenarčič, Brigita (Avtor)
ID Juliano, Luiz (Avtor)
ID Mehta, Shwetal (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
ID Lah Turnšek, Tamara (Avtor)
Datoteke:.pdf PDF - Predstavitvena datoteka, prenos (1,50 MB)
MD5: 0C77AF127CDD15F7B794A90908A4AB00
 
URL URL - Izvorni URL, za dostop obiščite https://doi.org/10.1016/j.bbamcr.2016.12.021
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek:Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1α (SDF-1α), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches. Furthermore, we aimed to prove that SDF-1α cleavage by CatK inactivates SDF-1α and inhibits the invasion of GSLCs. We performed mass spectrometric analysis of cleavage products of SDF-1α after proteolysis by CatK. We demonstrated that CatK cleaves SDF-1α at 3 sites in the N-terminus, which is the region of SDF-1α that binds to its receptors. Confocal imaging of human GBM tissue sections confirmed co-localization of SDF-1α and CatK in GSLC niches. In accordance, 2D and 3D invasion experiments using CXCR4/CXCR7-expressing GSLCs and GBM cells showed that SDF-1α had chemotactic activity whereas CatK cleavage products of SDF-1α did not. Besides, CXCR4 inhibitor plerixafor inhibited invasion of CXCR4/CXCR7-expressing GSLCs. In conclusion, CatK can cleave and inactivate SDF-1α. This implies that CatK activity facilitates migration of GSLCs out of niches. We propose that activation of CatK may be a promising strategy to prevent homing of GSLCs in niches and thus render these cells sensitive to chemotherapy and radiation.
Ključne besede:glioma stem-like cells, niche, stromal derived factor-[alpha], cathepsin K
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:01.03.2017
Leto izida:2017
Št. strani:str. 594-603
Številčenje:Vol. 1864, no. 3
PID:20.500.12556/DiRROS-19721 Novo okno
UDK:577.2
ISSN pri članku:0167-4889
DOI:10.1016/j.bbamcr.2016.12.021 Novo okno
COBISS.SI-ID:4162895 Novo okno
Datum objave v DiRROS:24.07.2024
Število ogledov:467
Število prenosov:303
Metapodatki:XML DC-XML DC-RDF
:
HIRA, Vashendriya V. V., VERBOVŠEK, Urška, BREZNIK, Barbara, SRDIČ, Matic, NOVINEC, Marko, KAKAR, Hala, WORMER, Jill, SWAAN, Britt van der, LENARČIČ, Brigita, JULIANO, Luiz, MEHTA, Shwetal, NOORDEN, Cornelis J. F. van in LAH TURNŠEK, Tamara, 2017, Cathepsin K cleavage of SDF-1[alpha] inhibits its chemotactic activity towards glioblastoma stem-like cells. Biochimica et biophysica acta : Molecular cell research [na spletu]. 2017. Vol. 1864, no. 3, p. 594–603. [Dostopano 4 april 2025]. DOI 10.1016/j.bbamcr.2016.12.021. Pridobljeno s: https://dirros.openscience.si/IzpisGradiva.php?lang=slv&id=19721
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Gradivo je del revije

Naslov:Biochimica et biophysica acta : Molecular cell research
Skrajšan naslov:Biochim. biophys. acta, Mol. cell res.
Založnik:Elsevier
ISSN:0167-4889
COBISS.SI-ID:5342727 Novo okno

Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0245-2015
Naslov:Ekotoksiologija, toksikološka genomika in karcinogeneza
Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0140-2015
Naslov:Proteoliza in njena regulacija
Financer:Drugi - Drug financer ali več financerjev
Program financ.:René Vogels travel grant (VVVH)
Financer:Drugi - Drug financer ali več financerjev
Program financ.:JoKolk scholarship (VVVH)
Financer:Drugi - Drug financer ali več financerjev
Program financ.:Dutch Cancer Society
Številka projekta:UVA 2014-6839
Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Program financ.:Young Researchers Grant
Financer:EC - European Commission
Program financ.:Fundação de Amparo à Pesquisa do Estado de São Paulo
Številka projekta:FAPESP-12/50191-AR

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

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