title: Possible involvement of tumor-producing VEGF-A in the recruitment of lymphatic endothelial progenitor cells from bone marrow.
abstract: Lymphatic metastasis of human malignant adenocarcinomas is a critical determinant of prognosis. Lymphangiogenesis, the growth of lymphatic vessels, is closely involved in lymphatic metastasis. However, the mechanisms of tumor lymphangiogenesis are not clearly understood. In a previous study, we showed that human gastric cancer MKN45 cells organize neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells in a nude mouse xenograft model. The present results also indicated that human colorectal cancer LS174T and breast cancer SK-BR-3 cells promoted lymphangiogenesis as well as the recruitment of lymphatic endothelial progenitor cells from bone marrow. Among growth factors, which are reported to be involved in lymphangiogenesis, only vascular endothelial growth factor (VEGF)-A was extensively secreted by these three types of adenocarcinoma cells in culture. The well-characterized lymphangiogenic factors VEGF-C and VEGF-D in the culture medium of these three types of adenocarcinoma cells were below the detectable levels in ELISA assay. Secretion of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) was not detected. In in vitro culture assay, VEGF-A directly induced the differentiation of bone marrow mononuclear cells into LYVE-1-positive lymphatic endothelial lineage cells. These data collectively suggest the possibility that VEGF-A-rich human adenocarcinomas induce tumor lymphangiogenesis via recruitment of lymphangiogenic endothelial progenitor cells from bone marrow.
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tawada
authors.affiliation: Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikegame
authors.affiliation: Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D006801:Humans; D042601:Lymphatic Vessels / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A