Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression

Nat Med. 1995 Feb;1(2):149-53. doi: 10.1038/nm0295-149.


In cancer patients, dormant micrometastases are often asymptomatic and clinically undetectable, for months or years, until relapse. We have studied dormant lung metastases under angiogenesis suppression in mice. The metastases exhibited rapid growth when the inhibition of angiogenesis was removed. Tumour cell proliferation, as measured by bromodeoxyuridine incorporation and immunohistochemical staining proliferating cell nuclear antigen, was not significantly different in dormant and growing metastases. However, tumour cells of dormant metastases exhibited a more than threefold higher incidence of apoptosis. These data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis*
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / secondary
  • Carcinoma, Lewis Lung / surgery
  • Cell Division / drug effects
  • Cyclohexanes
  • Fibrosarcoma / drug therapy
  • Fibrosarcoma / pathology
  • Fibrosarcoma / secondary
  • Fibrosarcoma / surgery
  • Lung / pathology
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis / pathology*
  • Neovascularization, Pathologic / physiopathology*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Organ Size
  • Proliferating Cell Nuclear Antigen / analysis
  • S Phase
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Proliferating Cell Nuclear Antigen
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol