title: Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages.
abstract: Fes is a protein tyrosine kinase with cell autonomous oncogenic activities that are well established in cell culture and animal models, but its involvement in human cancer has been unclear. Abundant expression of Fes in vascular endothelial cells and myeloid cell lineages prompted us to explore roles for Fes in the tumor microenvironment. In an orthotopic mouse model of breast cancer, we found that loss of Fes in the host correlated with reductions in engrafted tumor growth rates, metastasis, and circulating tumor cells. The tumor microenvironment in Fes-deficient mice also showed reduced vascularity and fewer macrophages. In co-culture with tumor cells, Fes-deficient macrophages also poorly promoted tumor cell invasive behavior. Taken together, our observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, in part by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages.
authors.affiliation: Division of Cancer Biology and Genetics, Department of Pathology and Molecular Medicine, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhang
authors.forename: Violeta
authors.initials: V
authors.lastname: Chitu
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Elliott
authors.forename: Peter A
authors.initials: PA
authors.lastname: Greer
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000235:genetics* / Q000378:metabolism; D055153:Stem Cell Niche / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D011505:Protein-Tyrosine Kinases; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes