MCF-10A CELLS INFECTED WITH THE INT-2 ONCOGENE INDUCE ANGIOGENESIS INTHE CHICK CHORIOALLANTOIC MEMBRANE AND IN THE RAT MESENTERY

A growing body of evidence demonstrates the relevant role of the int-2 (FGF-3) oncogene in human carcinomas. To investigate its angiogenic a ctivity, the human epithelial mammary cell line MCF-10A was infected w ith a retroviral expression vector carrying the int-2 oncogene. Infect ed cells were entrapped in an alginate pellet and placed on the chorio allantoic membrane of chick embryos. After 7 days, a dense capillary n etwork was found to grow toward the pellet, whereas parental cells did not show any angiogenic activity. Conditioned medium from int-2-infec ted cells was injected i.p. twice daily into rats over a period of 10 days. The mesentery of treated rats showed numerous small blood vessel s originating from larger vascular arcades and growing through the str omal layer of the mesentery. In control experiments, neither medium fo r cell culture nor conditioned medium from parental cells was found to induce angiogenesis. In conclusion, the stimulation of blood vessel g rowth by int-2-infected cells suggests that the production of the int- 2 protein is associated with the acquisition of the angiogenic phenoty pe.