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Titel: Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia
VerfasserIn: Schulze-Edinghausen, Lena
Dürr, Claudia
Öztürk, Selcen
Zucknick, Manuela
Benner, Axel
Kalter, Verena
Ohl, Sibylle
Close, Viola
Wuchter, Patrick
Stilgenbauer, Stephan
Lichter, Peter
Seiffert, Martina
Sprache: Englisch
Titel: Cancers
Bandnummer: 11
Heft: 6
Verlag/Plattform: MDPI
Erscheinungsjahr: 2019
Freie Schlagwörter: chronic lymphocytic leukemia
tumor microenvironment
progranulin
prognostic serum marker
cancer-associated fibroblasts
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Chronic lymphocytic leukemia (CLL) is known for its strong dependency on the tumor microenvironment. We found progranulin (GRN), a protein that has been linked to inflammation and cancer, to be upregulated in the serum of CLL patients compared to healthy controls, and increased GRN levels to be associated with an increased hazard for disease progression and death. This raised the question of whether GRN is a functional driver of CLL. We observed that recombinant GRN did not directly affect viability, activation, or proliferation of primary CLL cells in vitro. However, GRN secretion was induced in co-cultures of CLL cells with stromal cells that enhanced CLL cell survival. Gene expression profiling and protein analyses revealed that primary mesenchymal stromal cells (MSCs) in co-culture with CLL cells acquire a cancer-associated fibroblast-like phenotype. Despite its upregulation in the co-cultures, GRN treatment of MSCs did not mimic this effect. To test the relevance of GRN for CLL in vivo, we made use of the Eμ-TCL1 CLL mouse model. As we detected strong GRN expression in myeloid cells, we performed adoptive transfer of Eμ-TCL1 leukemia cells to bone marrow chimeric Grn−/− mice that lack GRN in hematopoietic cells. Thereby, we observed that CLL-like disease developed comparable in Grn−/− chimeras and respective control mice. In conclusion, serum GRN is found to be strongly upregulated in CLL, which indicates potential use as a prognostic marker, but there is no evidence that elevated GRN functionally drives the disease.
DOI der Erstveröffentlichung: 10.3390/cancers11060822
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-280289
hdl:20.500.11880/30010
http://dx.doi.org/10.22028/D291-28028
ISSN: 2072-6694
Datum des Eintrags: 12-Nov-2020
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/2072-6694/11/6/822/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Innere Medizin
Professur: M - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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