Prophylactical Low Dose Whole-Liver Irradiation Inhibited Colorectal Liver Metastasis by Regulating Hepatic Niche in Mice.

摘要: Background The liver is the most common target for metastatic colorectal cancer. Changes of local hepatic niche due to diseases such as cirrhosis decrease incidence cancer metastasis. Hepatic heterogeneity could influence risk Materials and methods We simulated changes via prophylactical irradiation with a safe dose 6 Gy. GEO dataset GO analysis revealed difference in expression matrix metalloproteinase 1 (MMP1) primary versus metastasis, well synchronous metachronous Western blotting, Immunofluorescence qRT-PCR were conducted measure protein expressions, location RNA expressions. Colony formation, wound-healing, transwell assays experiments performed determine malignant biological properties cells. shRNA transfection was used conduct stable transfected cell lines. Results Tissue inhibitor metalloproteinases (TIMP1) significantly higher metastases lesions than tumors. In vivo, TIMP1 increased after Gy irradiation, along MMP1 decreased, leading collagen fiber deposition impairment microcirculation. vitro, irradiated stellate cells-conditioned media reduced migration clone formation ability colon cells SW480 HCT116. Low tumor invasion migration. Conclusion Prophylactical whole-liver inhibit metastasis by regulating TIMP1/MMP1 balance before lesion formed.