Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Thoracic oncology

Abstract

Granulocyte-colony-stimulating factor (G-CSF) and macrophage-colony-stimulating factor (M-CSF) are used to treat myelosuppressed patients induced by antitumor chemotherapy. G-CSF and M-CSF are also known to stimulate growth of some nonhematopoetic tumor cells. Various mechanisms have been implicated in the progression of tumor growth. However, the contribution and the mechanism of G-CSF and M-CSF to tumor growth remain largely unknown. In this study, we determined whether G-CSF and M-CSF affect the tumor growth through activation of angiogenesis by inoculating Lewis Lung Carcinoma (LLC) cells into mice subcutaneously. Compared with non-treated mice, the growth of LLC cells was increased in G-CSF or M-CSF treated mice. The intratumoral vessels were confirmed by immunohistochemistry using antibody against factor VIII, and the vessel density was increased in G-CSF and M-CSF treated mice. G-CSF or M-CSF did not increase the growth of LLC cells in vitro. LLC cells were implanted into LacZ transgenic mice and stained to detect LacZ and factor VIII simultaneously. Intratumoral vessels were stained with LacZ, indicating vessels were derived from the host. Moreover, treatment of vascular endothelial growth factor (VEGF) receptor kinase inhibitor SU1498 impaired the tumor growth effect of G-CSF and M-CSF. These findings suggest that the G-CSF and M-CSF progress the tumor growth presumably by regulating the angiogenesis. Thus, manipulating myelosuppressed patients with G-CSF or M-CSF might be accompanied with adverse effect of residual tumor progression.

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T. Okazaki, S. Ebihara, H. Takahashi, A. Kanda, H. Sasaki (Sendai, Japan). The growth of lung cancer cells is progressed by G-CSF and M-CSF due to activation of angiogenesis. Eur Respir J 2003; 22: Suppl. 45, 1504

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