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

Nature Medicine volume 1, pages 149–153 (1995)Cite this article

Abstract

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.

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Authors and Affiliations

  1. Department of Surgery, Children's Hospital, and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Lars Holmgren, Michael S. O'Reilly & Judah Folkman

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  1. Lars Holmgren
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  2. Michael S. O'Reilly
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  3. Judah Folkman
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Holmgren, L., O'Reilly, M. & Folkman, J. Dormancy of micrometastases: Balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1, 149–153 (1995). https://doi.org/10.1038/nm0295-149

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