Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages

Koji Hiraoka, Michihisa Zenmyo, Kosuke Watari, Haruo Iguchi, Abbas Fotovati, Yusuke N. Kimura, Fumihito Hosoi, Takanori Shoda, Kensei Nagata, Hiroyuki Osada, Mayumi Ono, Michihiko Kuwano

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Abstract

Attention has recently focused on the critical role of inflammatory responses in the tumor stroma that provide favorable conditions for cancer-cell growth and invasion/metastasis. In particular, macrophages recruited into the tumor stroma and activated, known as tumor-associated macrophages, are suggested to promote tumorigenesis. In this study, we examined the effect of a decrease in the number of monocytes/macrophages in peripheral blood and the tumor stroma on the development of bone and muscle metastases by lung cancer cells. Treatment with clodronate encapsulated by liposomes (Cl2MDP-LIP) has been developed for the depletion of monocytes/macrophages in an animal model. Subcutaneous administration of Cl2MDP-LIP markedly reduced the number of monocytes in peripheral blood, resulting in efficient suppression of both bone metastasis and muscle metastasis when lung cancer HARA-B cells were injected into the left cardiac ventricle of mice. Treatment with Cl2MDP-LIP significantly reduced the number of macrophages in tumors and the number of osteoclasts in bone marrow, as well as peripheral monocytes in mice harboring lung cancer cells. In contrast, treatment with an osteoclast-targeting antibiotic, reveromycin A, inhibited bone metastasis by lung cancer cells, but not muscle metastasis. The survival of human macrophages in culture was found to be specifically blocked by Cl2MDP-LIP, but not by reveromycin A. Cl2MDP-LIP thus exerted antimetastatic effects in both bone and muscle whereas reveromycin A did so only in bone. Liposome-encapsulated bisphosphonate may modulate metastasis through decreasing the number of monocytes/macrophages in both peripheral blood and the tumor stroma, suggesting that tumor-associated macrophages might be suitable targets for antimetastatic therapy.

Original languageEnglish
Pages (from-to)1595-1602
Number of pages8
JournalCancer Science
Volume99
Issue number8
DOIs
Publication statusPublished - Aug 25 2008

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Clodronic Acid
Monocytes
Lung Neoplasms
Macrophages
Neoplasm Metastasis
Bone and Bones
Muscles
Neoplasms
Osteoclasts
Liposomes
Heart Ventricles
Muscle Development
Bone Development
Diphosphonates
Therapeutics
Muscle Cells
Carcinogenesis
B-Lymphocytes
Animal Models
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. / Hiraoka, Koji; Zenmyo, Michihisa; Watari, Kosuke; Iguchi, Haruo; Fotovati, Abbas; Kimura, Yusuke N.; Hosoi, Fumihito; Shoda, Takanori; Nagata, Kensei; Osada, Hiroyuki; Ono, Mayumi; Kuwano, Michihiko.

In: Cancer Science, Vol. 99, No. 8, 25.08.2008, p. 1595-1602.

Research output: Contribution to journalArticle

Hiraoka, K, Zenmyo, M, Watari, K, Iguchi, H, Fotovati, A, Kimura, YN, Hosoi, F, Shoda, T, Nagata, K, Osada, H, Ono, M & Kuwano, M 2008, 'Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages', Cancer Science, vol. 99, no. 8, pp. 1595-1602. https://doi.org/10.1111/j.1349-7006.2008.00880.x
Hiraoka, Koji ; Zenmyo, Michihisa ; Watari, Kosuke ; Iguchi, Haruo ; Fotovati, Abbas ; Kimura, Yusuke N. ; Hosoi, Fumihito ; Shoda, Takanori ; Nagata, Kensei ; Osada, Hiroyuki ; Ono, Mayumi ; Kuwano, Michihiko. / Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. In: Cancer Science. 2008 ; Vol. 99, No. 8. pp. 1595-1602.
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