Characteristic Patterns of VEGF, Integrins, ER.ALPHA. and HER2 Immunoreactivity Suggest Two Tumor Cell Populations in DMBA-Induced Rat Mammary Tumor

Abstract

Recent evidence has shown that certain tumors have characteristic cell populations related to tumor progression. Therefore, we investigated tumor cell populations in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumor, an established estrogen-sensitive angiogenic tumor model. The tumors pathologically identified as invasive ductal carcinoma were immunostained using antibodies against the following various molecules: vascular endothelial growth factor (VEGF), integrins, estrogen receptor alpha (ERα), human epidermal growth factor receptor-2 (HER2), p27, and laminin, all of which are known to be related to tumor progression, proliferation and/or prognosis. The basal layer, the outermost layer of tumor lobules facing the basement membrane, was mainly VEGF and integrin (α3, α6, β1) positive. In contrast, the inner layer, the internal cell layers of the tumor lobules, was mainly ERα and HER2 positive. The p27-positive rate in the inner layer was similarly low to that in the basal layer, suggesting a similar high proliferative potency between these layers. Laminin was positive in the basement membrane surrounding the tumor lobules. These results suggest that the tumor lobules consist of at least two cell populations, the basal and inner layers, with respect to the expression of VEGF, integrins, ERα and HER2; and that these cell populations may have distinct functions in the pathophysiology of this mammary tumor.