Ninck Simon, Reisser Christoph, Dyckhoff Gerhard, Helmke Burkhard, Bauer Harald, Herold-Mende Christel
Department of Head and Neck Surgery, University of Heidelberg, Germany.
Int J Cancer. 2003 Aug 10;106(1):34-44. doi: 10.1002/ijc.11188.
Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has become a major target in experimental cancer therapies. This therapeutical approach requires a profound knowledge of growth factor profiles that contribute to tumor growth and progression. The respective knowledge is presently rather incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we studied expression of several angiogenic cytokines including VEGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in HNSCC in vivo and in vitro. In tumor tissues expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 15 tissue-corresponding HNSCC cultures revealed that VEGF, PDGF-AB and less frequently GM-CSF were secreted in high amounts of up to 13 ng/ml/10(6) cells. Twenty percent of the HNSCC cultures expressed only 1 cytokine in biologically active amounts, 60% 2 or 3 and 20% expressed the maximum of 4 cytokines simultaneously. Interestingly, we observed a distinct cytokine pattern: HNSCC cells secreting only 1 or 2 cytokines presented always with either VEGF and/or PDGF-AB, while G-CSF and GM-CSF were secreted primarily together with VEGF and PDGF-AB. The number of cytokines expressed by HNSCC cells correlated with the microvessel density of the original tumor and with the clinical outcome: tumors producing at least 3 cytokines revealed a significantly poorer patient prognosis. Our data indicate a major role for VEGF and PDGF-AB in HNSCC and that the additional secretion of G-CSF or GM-CSF might contribute to a poorer prognosis in patients suffering from these tumors.
通过阻断血管生成细胞因子或其信号通路来抑制血管生成已成为实验性癌症治疗的主要靶点。这种治疗方法需要深入了解促成肿瘤生长和进展的生长因子谱。目前，关于头颈部鳞状细胞癌（HNSCC）的相关知识还相当不完整。因此，我们研究了几种血管生成细胞因子，包括VEGF、bFGF、PDGF-AB、PDGF-BB、G-CSF和GM-CSF在HNSCC体内和体外的表达情况。在肿瘤组织中，所有细胞因子均有表达，尽管在强度和分布模式上存在明显差异。对15种与组织相对应的HNSCC培养物上清液中的细胞因子进行定量分析发现，VEGF、PDGF-AB以及较少见的GM-CSF以高达13 ng/ml/10(6)细胞的大量分泌。20%的HNSCC培养物仅以生物活性量表达1种细胞因子，60%表达2种或3种，20%同时表达最多4种细胞因子。有趣的是，我们观察到一种独特的细胞因子模式：仅分泌1种或2种细胞因子的HNSCC细胞总是同时表达VEGF和/或PDGF-AB，而G-CSF和GM-CSF主要与VEGF和PDGF-AB一起分泌。HNSCC细胞表达的细胞因子数量与原发肿瘤的微血管密度以及临床结果相关：产生至少3种细胞因子的肿瘤患者预后明显较差。我们的数据表明VEGF和PDGF-AB在HNSCC中起主要作用，并且G-CSF或GM-CSF的额外分泌可能导致这些肿瘤患者预后更差。
