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| Status |
Public on Dec 31, 2014 |
| Title |
Hypoxia-induced stem-like cancer cells resistance to VEGFR inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome variation profiling by genome tiling array
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| Summary |
Developing strategies to overcome the frequent resistance to VEGF/VEGFR inhibitors in patients is a major challenge in antiangiogenic therapy for cancer. Targeting the VEGF pathway in vivo induces hypoxia and therefore enables to study drug-induced hypoxia in tumors. Hypoxia also occurs in the spontaneous evolution of cancers, particularly around areas of necrosis. Using cell markers such as CD133, CXCR4, or ALDH1, we identified stem-like cells in peri-necrotic areas in human biopsies and xenografts models of renal cancers. These stem-like cells were able in vitro to self-renew, form carcinoma spheres and had a tumorigenic potency, thus showing characteristics of stem-like cancer cells. In xenografted human renal cell carcinoma, we further demonstrated a strong link between necrosis, either spontaneous or treatment-induced, and the presence of CD133/CXCR4 double positive stem-like cells. Hypoxia increased their tumorigenic potency, induced overexpression of metallothionein2A, which we here identified as critical regulator of resistance to VEGFR-inhibition.
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| Overall design |
6 sample were collected and analysed for gene expression: 2 samples are human tumors xenografted into nude mice, 2 samples are human tumor renal kidney spheres cultured under hypoxic conditions and 2 other samples are human tumor renal kidney spheres cultured under normoxic conditions
Two DNA samples were analysed with CGH array : 1 tumor stem cell cultured in normoxic condition and one human renal carcinoma xenografted into nude mice.
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| Contributor(s) |
Varna M, Bousquet G, Feugeas J, Gapihan G, Ferreira I, Leboeuf C, Setterblad N, Duval A, Mongiat-Artus P, Bertheau P, Germain S, Janin A |
| Citation missing |
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| Submission date |
Sep 27, 2011 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Anne Janin |
| E-mail(s) |
jean-paul.feugeas@sls.aphp.fr
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| Phone |
+33142494012
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| Organization name |
University Paris 7, INSERM, APHP
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| Street address |
1 Av C Vellefaux
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| City |
Paris |
| ZIP/Postal code |
75010 |
| Country |
France |
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| Platforms (2) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA146383 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32414_RAW.tar |
91.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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