Proangiogenic effects of ionizing irradiation on squamous cell carcinoma of the hypopharynx.
OBJECTIVE
There is experimental evidence that ionizing irradiation affects a proangiogenic response. However, the relevance of this effect on tumour growth in vivo is not in detail investigated yet. The present objectives were to examine the influence of ionizing radiation on the expression of the vascular endothelial growth factor (VEGF) and its receptors (flt-1 and flk-1), the microvessel density and the tumour proliferation, in head and neck squamous cell carcinoma (HNSCC).


METHODS
We used a HNSCC-cell line, derived from a hypopharyngeal tumour, for subcutaneous injection in 16 athymic nude mice. After reaching an average diameter of 12-14 mm the xenografts were randomised and 8 out of the 16 animals (therapy group) were irradiated with a single fraction of 6 Gy while the control group remained without any intervention. The irradiated and the respective control tumours were prepared after 7 (T7) and 70 days (T70) for immunohistochemical analysis. The expression of VEGF, its receptors flk-1 and flt-1, the vessel density (CD31) and the proliferation rate (Ki67) were quantified.


RESULTS
At the point of time T7 we observed a reduction of the tumour growth rate, of the proliferative activity and of the VEGF- as well as of the VEGF-R-expression. At the point of time T70 we found increased values for proliferation, microvessel density, VEGF- and flk-1 expression in the therapy group compared to the therapy group at T7 as well as to the control group at T70.


CONCLUSIONS
These changes might suggest a long-term proangiogenic effect of irradiation, which might result in growth promotion of the remaining tumour after the end of therapy.
Koutsimpelas
D
D
Department of Otorhinolaryngology, University Hospital of Mainz, Langenbeckstr. 1, Mainz, Germany. koutsimpelas@hno.klinik.uni-mainz.de
Brieger
J
J
Kim
D W
DW
Stenzel
M
M
Hast
J
J
Mann
W J
WJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000528:radiation effects*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010039:Otorhinolaryngologic Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2