Involvement of CXCL14 in osteolytic bone metastasis from lung cancer

Takiguchi,Soichi; Korenaga,Natsuki; Inoue,Kazuko; Sugi,Erika; Kataoka,Yasufumi; Matsusue,Kimihiko; Futagami,Koujiro; Li,Yin-Ji; Kukita,Toshio; Teramoto,Norihiro; Iguchi,Haruo

doi:10.3892/ijo.2014.2293

Involvement of CXCL14 in osteolytic bone metastasis from lung cancer

Authors:
- Soichi Takiguchi
- Natsuki Korenaga
- Kazuko Inoue
- Erika Sugi
- Yasufumi Kataoka
- Kimihiko Matsusue
- Koujiro Futagami
- Yin-Ji Li
- Toshio Kukita
- Norihiro Teramoto
- Haruo Iguchi
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Affiliations: Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, Japan, Department of Pharmacy, Fukuoka University Hospital, Fukuoka 814-0180, Japan, Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan, Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan, Division of Pathology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan, Clinical Research Institute, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan
Published online on: February 10, 2014 https://doi.org/10.3892/ijo.2014.2293
Pages: 1316-1324

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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.

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