Malignant progression of a weakly malignant rat mammary tumor cell line, ER-1, by tumor microenvironmental factors.

ABSTRACT

Malignant progression is the process by which tumor cells acquire more malignant properties, such as invasiveness and metastasis, during tumor development. The process is thought to be regulated by the microenvironment surrounding tumor cells, which can modify the malignant properties of tumor cells directly or through various humoral factors. Using a cloned weakly malignant cell line, ER-1, which we established, we demonstrated that growth factors such as epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) derived from host cells play an important role in promoting malignant progression of ER-1 cells. It is noteworthy that EGF treatment induced not only reversible but also irreversible progression to ER-1 cells depending on the treatment period. An increase in intracellular reactive oxygen species by EGF stimulation was thought to be one of the key factors involved in EGF-induced malignant progression of ER-1 cells. Morphological investigations revealed that ER-1 cells that had acquired malignant properties showed more abundant microvilli on the surface compared to ER-1 cells. Thus, the ER-1 cell line is a useful tool for biological and morphological analyses of the mechanisms of malignant progression of tumor.