title: Involvement of CXCL14 in osteolytic bone metastasis from lung cancer.
abstract: To investigate the molecular mechanisms of lung cancer-induced bone metastasis, we established a bone-seeking subclone (HARA-B4) from a human squamous lung cancer cell line (HARA) using an in vivo selection method. We compared comprehensive gene expression profiles between HARA and HARA-B4, and identified the critical factors for the formation of bone metastasis using in vitro and in vivo assays. The number of bone metastatic colonies in the hind legs was significantly higher in HARA-B4-inoculated mice than in HARA-inoculated mice at 4 weeks after inoculation. In addition, visceral (adrenal) metastases were not found in HARA-B4-inoculated mice at autopsy, suggesting an increase in cancer cell tropism to bone in HARA-B4. Based on a comprehensive gene expression analysis, the expression level of CXC chemokine ligand 14 (CXCL14) was 5-fold greater in HARA-B4 than in HARA. Results of a soft agar colony formation assay showed that anchorage-independent growth ability was 4.5-fold higher with HARA-B4 than with HARA. The murine pre-osteoblast cell line MC3T3-E1 and the pre-osteoclast/macrophage cell line RAW264.7 migrated faster toward cultured HARA-B4 cells than toward HARA cells in a transwell cell migration assay. Interestingly, CXCL14 was shown to be involved in all events (enhancement of cancer cell tropism to the bone, anchorage-independent growth and/or recruitment of bone marrow cells) based on siRNA experiments in HARA-B4 cells. Furthermore, in clinical specimens of lung cancer-induced bone metastasis, expression of CXCL14 was observed in the tumor cells infiltrated in bone marrow in all specimens examined. CXCL14 was able to promote bone metastasis through enhancement of cancer cell tropism to the bone and/or recruitment of bone marrow cells around metastatic cancer cells.
authors.affiliation: Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Takiguchi
authors.affiliation: Department of Pharmacy, Fukuoka University Hospital, Fukuoka 814-0180, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Korenaga
authors.affiliation: Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Sugi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Matsusue
authors.affiliation: Department of Pharmacy, Fukuoka University Hospital, Fukuoka 814-0180, Japan.
authors.forename: Koujiro
authors.initials: K
authors.lastname: Futagami
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yin-Ji
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kukita
authors.affiliation: Division of Pathology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Teramoto
authors.affiliation: Clinical Research Institute, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D010014:Osteolysis / Q000150:complications / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D034741:RNA, Small Interfering