Occurrence of thymosin β4 in human breast cancer cells and in other cell types of the tumor microenvironment

Previous studies have shown that the G-actin sequestering polypeptide thymosin β4 frequently is overexpressed in cancers and that such overexpression correlates to malignant progression. However, the localization of thymosin β4 in human cancers has not been determined. We now demonstrate that there is a considerable heterogeneity in the cellular distribution of thymosin β4 in breast cancer. In most tumors examined, cancer cells showed low or intermediate reactivity for thymosin β4, whereas leukocytes and macrophages showed intense reactivity. In addition, endothelial cells showed variable reactivity to thymosin β4, whereas myofibroblasts were negative. There was no correlation between the intensity of tumor cell staining and histological grade, whereas there was a tendency toward a correlation between endothelial cell staining and grade. These results demonstrate that multiple cell types within the tumor microenvironment produce thymosin β4 and that such expression varies from tumor to tumor. Such heterogeneity of expression should be taken into account when the role of thymosin β4 in tumor biology is assessed.