Models of progression spanning preneoplasia and metastasis: The human MCF10AneoT.TGn series and a panel of mouse mammary tumor subpopulations

Abstract

Progression in human breast cancer is often depicted as the loss of estogen receptor expression as cancers shift from hormone-responsive/dependent to hormone-independent phenotypes. The narrowness of this definition stems from the obvious importance of this stage in progression in terms of prognosis and hormonal therapeutic approaches. Other investigators tend to view progression as initiation and promotion events, loss of contact inhibition and/or anchorage dependence in vitro, changes in growth factor requirements in vitro, acquirement of invasive capabilities, acquirement of metastatic phenotype, or transition from hyperplastic preneoplastic to neoplastic lesions. Of course, progression is a continuum of all these events from the first alteration of a normal epithelial cell, to the preneoplastic cell, to the ultimately lethal metastatic cell. We have developed two models that span the full spectrum of progression, one a human preneoplastic model and one a panel of closely related sister subpopulations derived from a single mouse mammary tumor that metastasize by different routes or fail to metastasize at different sequential steps of metastasis.