Nerve growth factor links oral cancer progression, pain, and cachexia.
Nerve growth factor links oral cancer progression, pain, and cachexia.
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DOI：
10.1158/1535-7163.mct-11-0123
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发表时间：
2011-09
影响因子：
5.7
通讯作者：
Schmidt BL
中科院分区：
文献类型：
--
作者：
Ye Y;Dang D;Zhang J;Viet CT;Lam DK;Dolan JC;Gibbs JL;Schmidt BL
癌症通常会引起剧烈的疼痛和快速的体重减轻，严重降低癌症患者的生活质量。癌症引起的疼痛和恶病质通常被独立地研究和治疗，尽管这两种症状与慢性炎症和促炎细胞因子的持续产生密切相关。由于神经生长因子（NGF）在炎症和疼痛中起着至关重要的作用，并且因为它与多种促炎细胞因子相互作用，我们假设NGF作为参与癌症相关炎症协调的关键内源性分子。神经生长因子可能是一种共同的机制，负责临床独特的癌症症状，如疼痛和恶病质以及癌症进展的分子。在这里，我们报道了NGF在人口腔鳞状细胞癌肿瘤和细胞培养物中高度升高。使用两种经验证的小鼠癌症模型，我们进一步证明了NGF阻断通过协调促炎细胞因子和瘦素产生来降低肿瘤增殖、伤害感受和体重减轻。NGF阻断还降低了伤害感受受体TRPV 1、TRPA 1和PAR-2的表达水平。总之，这些结果确定NGF是口腔癌中增殖、疼痛和恶病质之间的共同联系。抗神经生长因子可能成为治疗口腔癌及其相关症状的一种重要机制。
Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of pro-inflammatory cytokines. Since nerve growth factor (NGF) plays a cardinal role in inflammation, and pain, and because it interacts with multiple pro-inflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further demonstrated that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating pro-inflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms.