title: Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages.
abstract: Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcinoma cell lines. SP-A gene transduction suppressed the progression of tumor in subcutaneous xenograft or lung metastasis mouse models. Immunohistochemical analysis showed that the number of M1 antitumor tumor-associated macrophages (TAMs) was increased and the number of M2 tumor-promoting TAMs was not changed in the tumor tissue produced by SP-A-expressing cells. In addition, natural killer (NK) cells were also increased and activated in the SP-A-expressing tumor. Moreover, SP-A did not inhibit tumor progression in mice depleted of NK cells. Taking into account that SP-A did not directly activate NK cells, these results suggest that SP-A inhibited lung cancer progression by recruiting and activating NK cells via controlling the polarization of TAMs.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Sho
authors.initials: S
authors.lastname: Tabata
authors.forename: Sawaka
authors.initials: S
authors.lastname: Yukishige
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Masaki
authors.initials: M
authors.lastname: Hanibuchi
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Atsuro
authors.initials: A
authors.lastname: Saijo
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aono
authors.forename: Hisanori
authors.initials: H
authors.lastname: Uehara
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.forename: Julie G
authors.initials: JG
authors.lastname: Ledford
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D037662:Pulmonary Surfactant-Associated Protein A