Myeloid heme oxygenase-1 promotes metastatic tumor colonization in mice.
Bottom Line: Whether HO-1 has an effect on cancer progression through stromal compartments is less clear.Mechanistic studies revealed that HO-1 impacted chemoattractant-induced myeloid cell migration by modulating p38 kinase signaling.These data support a pathological role of myeloid HO-1 in metastasis and suggest a possibility of targeting myeloid HO-1 for cancer treatment.
Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, China.Show MeSH
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Mentions: The vascular permeability is crucial for tumor cell extravasation at the metastatic site. VEGF, a potent inducer of endothelial permeability, is induced by HO-1 in macrophages.20 We confirmed the previous finding that VEGF gene expression was significantly higher in WT-BMDM than HO-1+/−-BMDM (Fig. S5). To test whether macrophage-derived VEGF impacts tumor cell extravasation, we performed an in vitro transendothelial migration assay. As shown in Figure6(a), WT BMDM-CM induced significantly greater transendothelial migration of CMFDA-labeled B16F10 cells than HO-1+/− BMDM-CM. Cotreatment with VEGF neutralizing antibody, but not control IgG, resulted in the reduction of increased transendothelial migration of tumor cells induced by BMDM-CM (Fig.6b). These observations support the involvement of HO-1-induced VEGF in macrophage-mediated tumor cell extravasation at the metastatic site.
Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, China.