Role of angiogenesis in tumor growth and metastasis☆,☆☆
Section snippets
The role of vasculature in cancer growth
Autopsy studies in accident victims show that the incidence of in situ tumors, particularly those of the breast, prostate, and thyroid gland, is substantially higher than the documented prevalence of cancer,3 indicating that tumor metastasis is a relatively infrequent phenomenon. It has been proposed that the low metastatic activity of in situ tumors may be related to the fact that they have not acquired an angiogenic phenotype (ability to recruit vasculature), because tumor growth and
The angiogenic switch
The change from a quiescent to an invasive phenotype is invariably accompanied by the acquisition of angiogenic properties (“angiogenic switch”) and vascularization of the tumor. In contrast to normal cells, which form a single layer around capillary blood vessels, multiple layers of tumor cells surround the microvasculature, effectively creating a capillary “cuff.” This dependence of tumor cells on endothelial cells, the target of angiogenic factors, may explain amplified arrest or killing of
Endogenous inhibitors of angiogenesis: Angiostatin and endostatin
Clinical and preclinical studies have shown that removal of primary tumors leads to rapid growth of previously dormant micrometastases,2, 16, 17 suggesting that primary tumors produce soluble factor(s) that suppress the growth of small tumors at remote sites. The first of these was identified as angiostatin, a 38-kd internal fragment of plasminogen,17 which was subsequently shown to also induce dormancy and regression of tumor xenografts.18 In preclinical studies, metastatic growth of secondary
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Supported by an unrestricted educational grant from Genentech BioOncology.
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Address reprint requests to Judah Folkman, MD, Children's Hospital, Hunnewell 103, 300 Longwood Ave, Boston, MA 02115.