Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids
Abstract
Tumor hypoxia has been attributed to play a crucial role in tumorigenesis and therapeutic resistance. Recently, it has been suggested that hypoxia leads to and maintains the undifferentiated state of tumor stem cells, thereby contributing to chemoresistance. The aim of the present study is to investigate the influence of hypoxia on the protein expression of a panel of stem cell and chemoresistance markers using in vivo-like multicellular tumor spheroids derived from a glioblastoma short-term culture with tumor stem cell properties (SJ-1) as well as a conventional glioblastoma cell line (U87). Spheroids were formed in 21% and 1% O(2) in serum-free medium. The immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67), and stem cell markers (CD133, podoplanin, Bmi-1, nestin, Sox-2) as well as markers related to chemoresistance (MGMT, TIMP-1, Lamp-1, MRP1, MDR-1). As spheroids derived in hypoxia were smaller than in normoxia, a set of experiments was included in which the culturing time of hypoxic spheroids was extended to obtain equally sized spheroids. The results showed that expression of HIF-1α and HIF-2α was increased in hypoxia, whereas Ki-67 was reduced. Expression of stem cell markers CD133, podoplanin, Bmi-1, and nestin was increased in hypoxia, whereas Sox-2 was increased in SJ-1 only. TIMP-1 and Lamp-1 were increased in both SJ-1 and U87. In conclusion, the tumor cell phenotype related to stemness, and thereby potentially to chemoresistance, se…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HIF-1α promotes neurosphere formation in SFM.
“which was documented to promote neurosphere formation in SFM [61].”
From Stress Response of Glioblastoma Cells Mediated by miR-17-5p Targeting PTEN and the Passenger Strand miR-17-3p Targeting MDM2 (2012) · cites this paper as [61]
Cites
Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects
Hockel, M., & Vaupel, P. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.4.266 · Cited by 2,662 · see citing works
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871 · see citing works
Glinsky, G. V., Berezovska, O., & Glinskii, A. B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23412 · Cited by 916 · see citing works
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438 · see citing works
Glicklis, R., Merchuk, J. C., & Cohen, S. (2004) · Biotechnology and Bioengineering · doi:10.1002/bit.20086 · Cited by 316 · see citing works
Senescence, apoptosis and therapy — cutting the lifelines of cancer
Schmitt, C. A. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1044 · Cited by 295 · see citing works
Daponte, A., Ioannou, M., Mylonis, I., Simos, G., Minas, M., Messinis, I. E., & Koukoulis, G. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-335 · Cited by 82 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Li, H., & Yang, B. B. (2012) · Oncotarget · doi:10.18632/oncotarget.810 · Cited by 117 · see citing works
- Authors
- Kolenda, J., Jensen, S. S., Aaberg-Jessen, C., Christensen, K., Andersen, C., Brünner, N., & Kristensen, B. W.
- Venue
- Journal of Neuro-Oncology
- Published
- 2010-09-11
- Volume
- 103
- Issue
- 1
- Pages
- 43-58
- ISSN
- 0167-594X
- 1573-7373
- Cited by
- 115
- References
- 7
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
