The heterogeneous subclones might be induced by cycling hypoxia which was aggravated along with the luminal A tumor growth

Abstract

BackgroundIn process of infiltrating growth in solid tumor, the tumor cells undergo a periodic hypoxia/reoxygenation (circulating hypoxia) microenvironment, which might be one of principle reasons to promote formation of tumor heterogeneity and treatment failure. Therefore, it is very important to study how the microenvironment of circulating hypoxia induces the heterogeneous subclones in tumors. Material and MethodsThe maximum cross-section of luminal A tumor (LAT) was selected for the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) and estrogen receptor-alpha (ER-alpha), and the correlation between it and tumor diameter was observed. The distribution of intratumoral micro-vessels were analyzed by 3D reconstruction and CD34 staining. A circulating hypoxia model of MCF-7 was established to detect the HIF-1alpha and ER-alpha. ResultsThere was a negative correlation between the expressions of ER-alpha and HIF-1alpha (c=−2.40; p = 0.044) in the LAT. As shown by 3D ultrasound image, there were less functional micro-vessels in the center than the periphery of tumor(P < 0.05). ER-alpha expression gradually decreased with the time course of cycling hypoxia, which is inversely related to the expression of HIF-1alpha. ConclusionLAT is composed of heterogeneous subclone cells which can be distinguished by ER-alpha and HIF-1alpha, which was closely related with cycling hypoxia microenvironment.