PMID- 23940516 OWN - NLM STAT- MEDLINE DCOM- 20140305 LR - 20220223 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 8 DP - 2013 TI - Radiation therapy-induced tumor invasiveness is associated with SDF-1-regulated macrophage mobilization and vasculogenesis. PG - e69182 LID - 10.1371/journal.pone.0069182 [doi] LID - e69182 AB - Radiation therapy (RT) remains the front-line treatment for high-grade gliomas; however, tumor recurrence remains the main obstacle for the clinical success of RT. Using a murine astrocytoma tumor cell line, ALTS1C1, the present study demonstrates that whole brain irradiation prolonged the survival of tumor-bearing mice, although the mice eventually died associated with increased tumor infiltration. Immunohistochemical (IHC) analysis indicated that RT decreased the microvascular density (MVD) of the primary tumor core, but increased the MVD of the tumor invasion front. RT also increased the number of tumor-associated macrophages (TAMs) and the expression of stromal cell-derived factor-1 (SDF-1) and hypoxia-inducible factor-1 (HIF-1) at the tumor invasion front. SDF-1 expression suppressed by siRNA (SDFkd tumors) showed a decrease in RT-enhanced tumor invasiveness, leading to prolonged survival of mice bearing these tumors. The invasion front in SDFkd tumors showed a lower MVD and TAM density than that in the islands of the control or irradiated ALTS1C1 tumors. Our results indicate that tumor-secreted SDF-1 is one key factor in RT-induced tumor invasiveness, and that it exerts its effect likely through macrophage mobilization and tumor revascularization. FAU - Wang, Shu-Chi AU - Wang SC AD - Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan. FAU - Yu, Ching-Fang AU - Yu CF FAU - Hong, Ji-Hong AU - Hong JH FAU - Tsai, Chien-Sheng AU - Tsai CS FAU - Chiang, Chi-Shiun AU - Chiang CS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130805 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Chemokine CXCL12) RN - 0 (Hypoxia-Inducible Factor 1) SB - IM MH - Animals MH - Cell Line, Tumor MH - Chemokine CXCL12/*metabolism MH - Glioma/*radiotherapy MH - Hypoxia-Inducible Factor 1/metabolism MH - Immunohistochemistry MH - Macrophages/*cytology/metabolism/radiation effects MH - Mice PMC - PMC3734136 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/08/14 06:00 MHDA- 2014/03/07 06:00 PMCR- 2013/08/05 CRDT- 2013/08/14 06:00 PHST- 2013/03/12 00:00 [received] PHST- 2013/06/05 00:00 [accepted] PHST- 2013/08/14 06:00 [entrez] PHST- 2013/08/14 06:00 [pubmed] PHST- 2014/03/07 06:00 [medline] PHST- 2013/08/05 00:00 [pmc-release] AID - PONE-D-13-10962 [pii] AID - 10.1371/journal.pone.0069182 [doi] PST - epublish SO - PLoS One. 2013 Aug 5;8(8):e69182. doi: 10.1371/journal.pone.0069182. Print 2013.