title: Role of pulmonary macrophages in initiation of lung metastasis in anaplastic thyroid cancer.
abstract: Several clinical studies have demonstrated that increased macrophage infiltration into tumors confers metastatic potential and poor prognosis in cancer. Preclinical studies are needed to develop new strategies for countering metastasis. Our study was designed to investigate the impact of pulmonary macrophages on lung metastasis of anaplastic thyroid cancer (ATC). ATC (CAL-62) and macrophage (Raw264.7) were transfected with the effluc (CAL-62/effluc, Raw264.7/effluc). Coculture and migration assays were used to assess the effect of Raw264.7 or THP1 (human macrophage) (or conditioned medium) on the proliferation and/or migration of CAL-62/effluc cells in vitro. The effect of clodro-lipo or PBS-lipo on macrophage depletion was confirmed in vitro and in vivo. CAL-62/effluc cells (1 × 10(6) ) were intravenously injected into nude mice 24 h after clodro-lipo or PBS-lipo administration. Effect of clodro-lipo on the lung metastasis of CAL-62/effluc was assessed by bioluminescence imaging (BLI). Micro computed tomography (micro-CT) and histology. BLI signals of CAL-62/effluc and Raw264.7/effluc increased to cell number. Raw264.7 cells and THP1 cells promoted CAL-62/effluc proliferation, and conditioned medium of Raw264.7 cells promoted CAL-62/effluc migration. Clodro-lipo significantly depleted pulmonary macrophages in vitro and in vivo. Intensity of BLI signals in ATC lung metastasis was weaker in the clodro-lipo group than PBS-lipo control. Micro-CT imaging and hematoxylin/eosin staining revealed smaller tumor masses in the clodro-lipo group than PBS-lipo control. Our findings indicate that pulmonary macrophages have an important role in initiation of lung metastasis of ATC. New therapeutic strategies that preclude initiation of pulmonary metastasis could potentially be developed by targeting pulmonary macrophages.
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.|Department of Radiology, Taian City Central Hospital, Taian, China.
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Prakash
authors.initials: P
authors.lastname: Gangadaran
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Kalimuthu
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea.|Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu, Republic of Korea. abc2000@knu.ac.kr.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D049409:Luciferases, Firefly / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D008163:Luminescent Measurements / Q000379:methods; D008175:Lung Neoplasms / Q000556:secondary*; D016676:Macrophages, Alveolar / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000067996:RAW 264.7 Cells; D065646:Thyroid Carcinoma, Anaplastic / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000473:pathology*
chemical_list: D049409:Luciferases, Firefly
keywords: clodronate; lung metastasis initiation; macrophage; thyroid cancer