Inhibition of CXCR7 extends survival following irradiation of brain tumours in mice and rats
| Autor: | Laurence Recht, Maksim Sinyuk, Justin D. Lathia, Jason Karamchandani, T. J. Schall, Robert D. Berahovich, J. C. Jaen, R. Al Omran, Richard M. Ransohoff, M. E T Penfold, Shie-Chau Liu, P. Zhang, J. P. Powers, Diane Tseng, Karen Ebsworth, Holbrook E Kohrt, M. J. Walters, Sophia B. Chernikova, J M Brown, Erin E. Mulkearns-Hubert, Milton Merchant, M. Kioi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Chemokine Pathology medicine.medical_specialty Angiogenesis Mice Nude CXCR4 vasculogenesis Rats Sprague-Dawley angiogenesis Mice Text mining Vasculogenesis medicine Animals Humans Receptors CXCR irradiation biology Brain Neoplasms business.industry chemokine glioblastoma CXCL12 medicine.disease CXCR7 Chemokine CXCL12 nervous system diseases Chemokine CXCL11 Rats 3. Good health Oncology Neoplastic Stem Cells biology.protein Neoplasm Recurrence Local Translational Therapeutics business Glioblastoma |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: In experimental models of glioblastoma multiforme (GBM), irradiation (IR) induces local expression of the chemokine CXCL12/SDF-1, which promotes tumour recurrence. The role of CXCR7, the high-affinity receptor for CXCL12, in the tumour's response to IR has not been addressed. Methods: We tested CXCR7 inhibitors for their effects on tumour growth and/or animal survival post IR in three rodent GBM models. We used immunohistochemistry to determine where CXCR7 protein is expressed in the tumours and in human GBM samples. We used neurosphere formation assays with human GBM xenografts to determine whether CXCR7 is required for cancer stem cell (CSC) activity in vitro. Results: CXCR7 was detected on tumour cells and/or tumour-associated vasculature in the rodent models and in human GBM. In human GBM, CXCR7 expression increased with glioma grade and was spatially associated with CXCL12 and CXCL11/I-TAC. In the rodent GBM models, pharmacological inhibition of CXCR7 post IR caused tumour regression, blocked tumour recurrence, and/or substantially prolonged survival. CXCR7 expression levels on human GBM xenograft cells correlated with neurosphere-forming activity, and a CXCR7 inhibitor blocked sphere formation by sorted CSCs. Conclusions: These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|