Prevention by delay: Nonspecific immunity elicited by IL-12 hinders Her-2/neu mammary carcinogenesis in transgenic mice

F. Cavallo, E. Di Carlo, E. Quaglino, M. Jezzi, M. Strasly, F. Bussolino, M. P. Colombo, P. Nanni, P. L. Lollini, P. Musiani, G. Forni

Research output: Contribution to journalArticlepeer-review

Abstract

As a natural consequence of the expression of the activated transforming rat Her-2/neu oncogene all mammary glands of female transgenic BALB/c (BALB-neuT) mice develop atypical epithelial hyperplasia which progresses to invasive carcinoma. A lobular carcinoma is palpable in all mammary glands of 33-week-old BALB-neuT mice. This progression is markedly delayed by systemic administration of IL-12. In a series of studies the best administration schedule, the lowest dose and the most effective administration time have been defined. The cellular and molecular mechanisms resulting in the delay of carcinogenesis have been established. By means of a series of downstream mediators IL-12 inhibits the angiogenic burst that goes along with the passage from preneoplastic to neoplastic and invasive lesions; it also recruits lymphoid cells in the mammary pad and activates their cytotoxicity towards neoplastic cells and newly formed vessels; and furthermore, it induces lymphoid cells to trigger antiagiogenic activities in neoplastic epithelial cells. Effective, low-dose and non-toxic IL-12 treatments may thus be envisaged as a possible option in the management of preneoplastic mammary lesions and in mammary cancer prevention.

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalJournal of Biological Regulators and Homeostatic Agents
Volume15
Issue number4
Publication statusPublished - 2001

Keywords

  • Antitumor vaccines
  • Cancer prevention
  • Carcinogenesis
  • ErbB-2
  • Her-2/neu oncogene

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Physiology (medical)
  • Medicine (miscellaneous)
  • Physiology
  • Agricultural and Biological Sciences(all)

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