Tumor response to radiotherapy regulated by endothelial cell apoptosis Academic Article uri icon


MeSH Major

  • Apoptosis
  • Endothelium, Vascular
  • Fibrosarcoma
  • Melanoma, Experimental
  • Proto-Oncogene Proteins c-bcl-2


  • 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.

publication date

  • May 16, 2003



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1082504

PubMed ID

  • 12750523

Additional Document Info

start page

  • 1155

end page

  • 9


  • 300


  • 5622