DORMANCY OF MICROMETASTASES - BALANCED PROLIFERATION AND APOPTOSIS INTHE PRESENCE OF ANGIOGENESIS SUPPRESSION

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 angioge nesis was removed. Tumour cell proliferation, as measured by bromodeox yuridine incorporation and immunohistochemical staining proliferating cell nuclear antigen, was not significantly different in dormant and g rowing metastases. However, tumour cells of dormant metastases exhibit ed a more than threefold higher incidence of apoptosis. These data sho w that metastases remain dormant when tumour cell proliferation is bal anced by an equivalent rate of cell death and suggest that angiogenesi s inhibitors control metastatic growth by indirectly increasing apopto sis in tumour cells.