Tumor angiogenesis is an important event in tumor malignancy; and the vasculature formed in tumor region is typically dysfunctional. Multiple factors are associated with tumor vessel abnormalities, but the precise mechanism has not been fully understood. In the present study, a tumor-containing cell sheet was prepared by mixing a small population of human embryonal rhabdomyosarcoma (RMS) cells (RDs) with human skeletal muscle myoblasts (HSMMs) to mimic muscle tissue invaded by RMS cells. Sheet fluidity and the extracellular matrix (ECM) meshwork of the tumor containing cell sheet were found to be elevated and disordered, demonstrating the disruptive effect of tumor cells on sheet structure. When green fluorescent protein expressing human umbilical vein endothelial cells (GFP-HUVECs) were co-cultured with the tumor-containing cell sheet, an endothelial network was formed, but degraded faster as a result of activated migration of endothelial cells in the tumor-containing cell sheet. This study suggested that disorganized tissue structure facilitate tumor angiogenesis by activation of endothelial cell migration. (C) 2017, The Society for Biotechnology, Japan. All rights reserved.