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G-CSF supplementation with chemotherapy can promote revascularization and subsequent tumor regrowth: prevention by a CXCR4 antagonist
| Content Provider | Scilit |
|---|---|
| Author | Voloshin, Tali Gingis-Velitski, Svetlana Bril, Rotem Benayoun, Liat Munster, Michal Milsom, Chloe Kerbel, Robert S. Shaked, Yuval |
| Copyright Year | 2011 |
| Description | Recombinant granulocyte colony-stimulating factor (G-CSF) is used to accelerate recovery from chemotherapy-induced myelosuppression. G-CSF has been recently shown to stimulate angiogenesis mediated by several types of bone marrow-derived cell populations. To investigate whether G-CSF may alter tumor response to therapy, we studied Lewis lung and EMT/6 breast carcinomas in mice treated with paclitaxel (PTX) chemotherapy in combination with G-CSF. We compared the results obtained to mice treated with PTX and AMD3100, a small-molecule drug antagonist of CXCR4 which, like G-CSF, can be used to mobilize hematopoietic cells. We show that PTX combined with G-CSF treatment facilitates revascularization, leading to an improvement in blood perfusion in LLC tumors, and a decrease in hypoxia in EMT/6 tumors, thus enhancing tumor growth in comparison to PTX or PTX and AMD3100 therapies. We found that hemangiocytes but not Gr-1+ CD11b+ cells colonize EMT/6 tumors after treatment with PTX and G-CSF, but not PTX and AMD3100, and therefore may contribute to angiogenesis. However, increases in hemangiocyte colonization were not observed in LLC PTX and G-CSF–treated tumors, suggesting distinct mechanisms of tumor revascularization after G-CSF. Overall, our observations suggest that despite its known considerable clinical benefits, G-CSF might contribute to tumor revascularization by various mechanisms, and diminish the antitumor activity of chemotherapy, an effect that can be prevented by AMD3100. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179406/pdf |
| Ending Page | 3435 |
| Page Count | 10 |
| Starting Page | 3426 |
| DOI | 10.1182/blood-2010-11-320812 |
| Journal | Blood |
| Issue Number | 12 |
| Volume Number | 118 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2011-09-22 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Angiogenesis Hematopoietic Cells Bone Marrow Recombinant Ptx Chemotherapy Mice Revascularization Amd3100 Csf Journal: Blood (Vol- 121, Issue- 12) |
| Content Type | Text |
| Resource Type | Article |
