Cancer-associated myofibroblasts possess various factors to promote endometrial tumor progression

Myofibroblastic Invasion associated with malignant epithelial cells of endo metrial cancer as well as other cancers is often found in the interstitium. To assess the myofibroblastic-epithelial interaction, frozen sections from a total of 10 endometrial cancers with or without invasive myofibroblasts were immunohistochemically examined. Interestingly, the invasive myofibrobl asts adjacent to malignant epithelial. cells showed frequently intensive po sitive staining of several growth factors such as vascular endothelial grow th factor (VEGF), insulin-like growth factor I, and epidermal growth factor , the cognate receptors such as Fetal liver kinase-1/Kinase Insert Domain-c ontaining receptor/VEGF receptor-2, fms-like tyrosine kinase-1/VEGF recepto r-1, and epidermal growth factor receptor, several cell cycle regulators su ch as cyclins and cyclin dependent kinases, and estrogen receptor alpha. Mo reover, we indicated that the majority of the myofibroblasts as well as can cer epithelial cells are proliferating because of their positive staining o f proliferating cell nuclear antigen and M-67. Furthermore, the myofibrobla sts were also positive of hypoxia-inducible factor 1 alpha, which is a mark er protein of hypoxia, probably followed by activation of VEGF-Flk-1 and VE GF-fms-like tyrosine kinase-1 signals, which could initiate angiogenesis. T hese findings suggest directly that the myofibroblasts might participate in the progression of tumor cells in terms of cancer cell growth stimulation and also activated initiation of angiogenesis.