In the microenvironment of the liver, CSCs promote pro-tumor TME formation in several ways, such as the production of the tissue inhibitor of metalloproteinase 1 (TIMP1) or the activation of the hepatocyte-derived growth factor/hepatocyte-derived growth factor receptor (HGF/HGFR) system by the hypoxia-induced activation of HIF1. The gene discussed is TIMP1; the disease is neoplasm.