Tumor response to radiotherapy regulated by endothelial cell apoptosis Journal Article
| Authors: | Garcia-Barros, M.; Paris, F.; Cordon-Cardo, C.; Lyden, D.; Rafii, S.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R. |
| Article Title: | Tumor response to radiotherapy regulated by endothelial cell apoptosis |
| Abstract: | About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range. |
| Keywords: | controlled study; proto-oncogene proteins; cancer growth; nonhuman; cancer patient; cancer radiotherapy; radiation dose; animal cell; mouse; phenotype; animals; mice; apoptosis; radiotherapy; animal experiment; animal model; patient monitoring; neovascularization, pathologic; wild type; radiation exposure; radiation response; animalia; endothelium cell; fibrosarcoma; endothelium, vascular; tumors; cancer cell; melanoma cell; melanoma, experimental; neoplasm transplantation; disease models, animal; bone marrow transplantation; microvasculature; proto-oncogene proteins c-bcl-2; sphingomyelin phosphodiesterase; hypothesis; radiation tolerance; cells; endothelial apoptosis; protein bax; in situ nick-end labeling; bcl-2-associated x protein; drug dosage; cancer; priority journal; article; response analysis |
| Journal Title: | Science |
| Volume: | 300 |
| Issue: | 5622 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2003-05-16 |
| Start Page: | 1155 |
| End Page: | 1159 |
| Language: | English |
| DOI: | 10.1126/science.1082504 |
| PUBMED: | 12750523 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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19Paris -
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300Kolesnick
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