Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor promote malignant growth of cells from head and neck squamous cell carcinomas in vivo
Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor promote malignant growth of cells from head and neck squamous cell carcinomas in vivo
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DOI：
10.1158/0008-5472.can-06-0158
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发表时间：
2006-08-15
期刊：
影响因子：
11.2
通讯作者：
Mueller, Margareta M.
中科院分区：
文献类型：
--
作者：
Gutschalk, Claudia M.;Herold-Mende, Christel C.;Mueller, Margareta M.
粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）用于改善癌症治疗诱导的中性粒细胞减少症和粘膜炎。然而，头颈部鳞状细胞癌（HNSCC）的第一个数据表明G-CSF治疗的长期预后受损，以前的研究表明这两个因素对人类上皮肿瘤的进展有贡献。因此，我们研究G-CSF和GMCSF在人HNSCC肿瘤细胞进展中的作用。两种因子均刺激从表达G-CSF和GM-CSF和/或其受体的患者肿瘤建立的肿瘤细胞系的增殖和迁移。在三维器官型培养模型中，G-CSF和GM-CSF的阻断抑制了肿瘤细胞的侵袭。这两个因素对肿瘤恶性程度的贡献在裸鼠体内移植中得到进一步证实。侵袭性和恶性生长产生与原始患者肿瘤相似的肿瘤表型，仅在表达G-CSF和GM-CSF的肿瘤中观察到，并与增强和持续的血管生成和增强的炎性细胞募集相关。虽然因子阴性肿瘤生长稍快，但其特征是缺乏侵袭，血管生成减少和短暂，以及大面积坏死。这些数据为G-CSF和GMCSF在人HNSCC中的进展促进作用提供了证据，并建议进一步详细评估其在这些肿瘤治疗中的用途。
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 GMCSF 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 GMCSF in human HNSCC and suggest further detailed evaluation of their use in the therapy of these tumors.