Angiogenic State Research Articles

Summary of Cancer Research Campaign Lecture

. Both strategies could be employed together . The validity of the latter strategy is being tested with novel angiogenesis inhibitors which have been developed recently . However, the former strategy has received little attention, mainly because a central question remains unanswered : 'When and how do tumours switch to the angiogenic state?' We have began to investigate this question . Because the switch to the angiogenic state is more clearly detected in human cancer than in animal tumours, we (Noel Weidner and Judah Folkman), studied the prevascular and vascular phases of tumour growth in women with invasive breast cancer, by quantitating vessel density in biopsy specimens stained with Factor VIII antibody . We found that the onset of angiogenesis behaves as an independent multifocal event . Angiogenic activity appears (1) in a subset of ducts at different times

Induction of angiogenesis during the transition from hyperplasia to neoplasia

It is now well established that unrestricted growth of tumours is dependent upon angiogenesis. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types is providing a new format for studying multi-step tumorigenesis. In one of these models, transgenic mice expressing an oncogene in the beta-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novel in vitro assay confirms that hyperplasia per se does not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenic in vitro at a time when such islets are neovascularized in vivo and at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.