In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1319-1319
Abstract:
The precise targeting and energy deposition characteristics of proton theapy have attracted considerable attention in the clinical oncology community. An increasing number of proton facilities are being established to exploit the physical advantages of this radiation for cancer treatment. However, the fact that there may also be biologically-based advantages for the use of protons has essentially been overlooked. We here demonstrate that proton irradiation inhibits expression of major pro-angiogenic factors and multiple angiogenesis-associated processes, including invasion and endothelial cell proliferation, which are critical to cancer progression. Dose-dependent suppression of angiogenic signaling was demonstrated for human tumor, fibroblasts and microvascular endothelial cells. Pan-genomic microarray analysis and RT-PCR revealed that post-irradiation (0.5, 1.0 2.0 Gy) critical pro-angiogenic signaling factors, including vascular endothelial growth factor (VEGF), interleukin 6 and 8 (IL-6, IL-8) and the hypoxia-inducible factor-1 alpha (HIF-1α), were significantly downregulated. Co-culture studies demonstrated proliferation and invasion of endothelial cells was inhibited by irradiation of both tumor and fibroblast cells, suggesting that proton irradiation may contribute to angiogenesis suppression through paracrine signalings from targeted cells as well as by direct action. Addition of recombinant IL-8 or VEGF partially restored these functions, once again indicating that suppression of these factors plays a functional role in inhibition of tumor progression. Finally an attenuated growth rate and a reduced invasive capacity was demonstrated in vivo for proton-irradiated human lung cancer, A549. Taken together, these findings provide novel preclinical evidence that proton irradiation may, in addition to its physical advantages, have important biological ramifications that should be a consideration in the optimization of proton therapy. This work was supported by NASA NSCOR grant #NNJ06HA28G Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1319.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-1319
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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