Data from MFG-E8/Lactadherin Promotes Tumor Growth in an Angiogenesis-Dependent Transgenic Mouse Model of Multistage Carcinogenesis
Year: 2023
Type: other
Abstract: The relevance of angiogenesis in tumor biology and as a therapeutic target is well established. MFG-E8 (also termed lactadherin) and developmental endothelial locus 1 (Del1) constitute a two-gene family of αvβ3/β5 ligands that regulate angiogenesis. After detecting MFG-E8 mRNA in murine tumor cell lines, we sought to determine if MFG-E8 influenced tumorigenesis in Rip1-Tag2 transgenic mice, a cancer model in which angiogenesis is critical. MFG-E8 mRNA and protein were increased in angiogenic islets and tumors in Rip1-Tag2 mice compared with normal pancreas. Frequencies of angiogenic islets and tumor burdens were decreased in MFG-E8–deficient Rip1-Tag2 mice compared with those in control Rip1-Tag2 mice. Invasive carcinomas were modestly underrepresented in MFG-E8–deficient mice, but tumor frequencies and survivals were comparable in these two strains. Absence of MFG-E8 also led to decreases in tumor vascular permeability without obvious changes in vascular morphology. Decreased proliferation was noted in angiogenic islets and increases in apoptotic cells were detected in islets and tumors. Compensatory increases in mRNA encoding proangiogenic proteins, including FGF2, in angiogenic islets, and Del1, in angiogenic islets and tumors, were also detected in MFG-E8–deficient mice. MFG-E8 and its homologue Del1 may represent relevant targets in cancer and other diseases in which angiogenesis is prominent. [Cancer Res 2007;67(14):6777–84]
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4361249980