Induction of angiogenesis during the transition from hyperplasia to neoplasia

Nature. 1989 May 4;339(6219):58-61. doi: 10.1038/339058a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma, Islet Cell / blood supply*
  • Adenoma, Islet Cell / genetics
  • Adenoma, Islet Cell / pathology
  • Animals
  • Endothelium, Vascular / pathology
  • Hyperplasia
  • Islets of Langerhans / blood supply*
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Transgenic
  • Neovascularization, Pathologic*
  • Oncogenes
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Precancerous Conditions*