Vascular Functional Imaging and Physiological Environment of Hyperplasia, Non-Metastatic and Metastatic Breast Cancer

摘要

Our goals were to understand the role of vascularization and physiological and metabolic properties in breast cancer metastasis using magnetic resonance (MR) imaging (I) and MR spectroscopy (S) of human breast cancer models. Key findings were: MR spectra of tumors revealed a significant differences in phospholipid composition and in intra- and extracellular pH, between control and transgene tumors formed by MDA-ME-435 human breast carcinoma cells transfected with nm23 constructs. These data demonstrate the potential of noninvasive MRS to detect forms of gene therapy which may involve transfection of cells with nm23. Choline phospholipid metabolite levels progressively increased in cultured human mammary epithelial cells (HMECs) as cells became more malignant. This work is relevant to diagnosis of breast cancer and provides a rationale for selective pharmacological intervention. Lactate levels increased significantly in cultured HMEC following malignant transformation and may promote invasive behavior and contribute to metastasis. 3-dimensional analysis of vascular volume and permeability and histological morphology demonstrated that areas of low vascular volume were associated with cell death and increasingly permeable vasculature. The more metastatic cell lines were characterized by higher vascular volume and permeability. These results indicate a potential use of MRI and MRS for evaluating metastatic risk' noninvasively.