Granulocyte Colony-stimulating Factor and Granulocyte-macrophage Colony-stimulating Factor Promote Malignant Growth of Cells from Head and Neck Squamous Cell Carcinomas in Vivo.
From: Group of Tumour and Microenvironment, German Cancer Research Centre, Heidelberg, Germany.
Cancer research
- Publish Date: Aug 2006
- ISSN: 1538-7445
- Volume: 66
- Issue: 16
- Pages: 8026-36
- Medium: Internet
- Language: English
- Citation (JAMA): Gutschalk Claudia M, Herold-Mende Christel C, Fusenig Norbert E, et al. Granulocyte Colony-stimulating Factor and Granulocyte-macrophage Colony-stimulating Factor Promote Malignant Growth of Cells from Head and Neck Squamous Cell Carcinomas in Vivo.. Cancer Res. Aug 2006;66:8026-36
Abstract
Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are used to ameliorate cancer therapy-induced neutropenia and mucositis. Yet, first data in head and neck squamous cell carcinoma (HNSCC) indicate an impaired long-term prognosis on G-CSF treatment, and previous studies showed a contribution of both factors to the progression of human epithelial tumors. Therefore, we investigate the role of G-CSF and GM-CSF in progression of tumor cells from human HNSCC. Both factors stimulated proliferation and migration of tumor cell lines established from patient tumors expressing G-CSF and GM-CSF and/or their receptors. Blockade of G-CSF and GM-CSF inhibited tumor cell invasion in a three-dimensional organotypic culture model. The contribution of both factors to tumor malignancy was further confirmed in nude mouse transplants in vivo. Invasive and malignant growth yielding a similar tumor phenotype as the original patient tumor was exclusively observed in G-CSF- and GM-CSF-expressing tumors and was associated with enhanced and persistent angiogenesis and enhanced inflammatory cell recruitment. Although factor-negative tumors grew somewhat faster, they were characterized by lack of invasion, reduced and transient angiogenesis, and large necrotic areas. These data provide evidence for a progression-promoting effect of G-CSF and GM-CSF in human HNSCC and suggest further detailed evaluation of their use in the therapy of these tumors.
Mesh Headings (Keywords): Animals, Carcinoma, Squamous Cell, Cell Division, Cell Movement, Granulocyte Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Head and Neck Neoplasms, Humans, Mice, Mice, Nude, RNA, Neoplasm, Reverse Transcriptase Polymerase Chain Reaction, Transplantation, Heterologous, Tumor Cells, Cultured
Check for Full Text / PubMed Unique Identifier (PMID): 16912178
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