title: Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment.
abstract: The organ microenvironment significantly affects the processes of cancer metastasis. Elucidating the molecular mechanisms of interaction between tumor cells and the organ microenvironment is crucial for the development of effective therapeutic strategies to eradicate cancer metastases. Macrophage stimulating protein (MSP), an activator of macrophages, regulates a pleiotropic array of effects, including proliferation, cellular motility, invasiveness, angiogenesis, and resistance to anoikis. However, the role of MSP in cancer metastasis is still largely unknown. In this study, the action of MSP on the production of metastases was determined in a multiple-organ metastasis model. The murine MSP gene was transfected into two human SCLC cell lines, SBC-5 and H1048, to establish transfectants secreting biologically active MSP. MSP gene transduction did not affect cell proliferation and motility in vitro. Intravenously inoculated MSP transfectants produced significantly larger numbers of liver metastases than parental cells or vector control clones, while there were no significant differences in bone or lung metastases among them. Immunohistochemical analyses of liver metastases revealed that tumor-associated microvessel density and tumor-infiltrating macrophages were significantly increased in lesions produced by MSP transfectants. MSP could stimulate the migration of murine macrophages and endothelial cells in vitro. Consequently, MSP may be one of the major determinants that affects the properties of tumor stroma and that produces a permissive microenvironment to promote cancer metastasis.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-8-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Seidai
authors.initials: S
authors.lastname: Sato
authors.forename: Masaki
authors.initials: M
authors.lastname: Hanibuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Nodoka
authors.initials: N
authors.lastname: Yamamori
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Ogawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Trung The
authors.initials: TT
authors.lastname: Van
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D059016:Tumor Microenvironment
chemical_list: D017931:DNA Primers; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor