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PERI‐ARTERIOLAR GLIOBLASTOMA STEM CELL NICHES EXPRESS BONE MARROW HEMATOPOIETIC STEM CELL NICHE PROTEINS
Author(s) -
Hira Vashendriya V.V.,
Molenaar Remco J.,
Khurshed Mohammed,
Van Noorden Cornelis J.F.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.407.6
Subject(s) - biology , ecological niche , stem cell , cd44 , niche , bone marrow , microbiology and biotechnology , immunology , cell , genetics , ecology , habitat
In glioblastoma, a fraction of malignant cells consists of therapy‐resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal derived‐factor 1α (SDF‐1α), C‐X‐C receptor type 4 (CXCR4), osteopontin (OPN) and cathepsin K (CatK) are expressed in hypoxic GSC niches around arterioles in 5 human glioblastoma samples. In HSC niches, HSCs are retained by binding of SDF‐1α and OPN to their receptors CXCR4 and CD44, respectively. Protease CatK cleaves SDF‐1α to release HSCs out of niches. The aim of the present study was to reproduce the immunohistochemical localization of these GSC markers in 16 human glioblastoma samples with the addition of 3 novel markers. Furthermore, we assessed the type of blood vessels associated with GSC niches. In total, we found 7 GSC niches containing CD133‐positive and nestin‐positive GSCs as a single‐cell layer exclusively around the tunica adventitia of 2% of the CD31‐positive and SMA‐positive arterioles and not around capillaries and venules. Niches expressed SDF‐1α, CXCR4, CatK, OPN, CD44, HIF‐1α and VEGF. In conclusion, we show that GSC niches are present around arterioles and express bone marrow HSC niche proteins. Support or Funding Information This study was financially supported by the Dutch Cancer Society (KWF; UVA 2014‐6839; VVVH, MK, RJM, CJFVN), René Vogels Foundation (VVVH), Jo Kolk Foundation (VVVH) and an AMC PhD scholarship (RJM).Representation of the GSC niche ( A, B ) and the HSC niche ( C, D ) showing that SDF‐1α /CXCR4 interactions and OPN/CD44 interactions at the arteriolar adventitia retain GSCs and HSCs in their niches and that CatK activity releases GSCs and HSCs out of the niche, so that GSCs and HSCs differentiate into progenitor cells and subsequently migrate out of the niche into the circulation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .