Roles of inflammation-driven chemokines in the pathogenesis of ovarian cancer

项目摘要/摘要 卵巢癌是女性癌症死亡的第五大原因，因为 致命的潜伏性疾病通常是无症状的，直到恶性程度达到 在卵巢之外。尽管确切的病因尚不清楚，但越来越多的 有证据表明，卵巢癌是一种与炎症相关的癌症 来自炎症性疾病。与正常卵巢上皮细胞相比，卵巢 肿瘤细胞高表达肿瘤坏死因子(TNF)作为主要促炎因子 直接或间接控制趋化因子网络的细胞因子。受生长调控 癌基因(CXCL1)在卵巢癌细胞中显著增加，在卵巢癌细胞中 卵巢癌患者的血浆和腹水。我们最近的研究结果是 CXCL1、2和8是主要的炎症驱动的趋化因子，主要产生和 大量来自卵巢癌细胞对炎症的反应。在其他系统中， CXCL1与其特异性受体(CXCR2)结合，发挥多种功能，如 细胞增殖、侵袭、肿瘤形成和血管生成，这可能在 卵巢癌的发病机制。这些事实支持炎症驱动的 趋化因子通过炎性肿瘤微环境促进卵巢癌 这会导致大量腹水和广泛的腹膜扩散，如 晚期卵巢癌死亡率居高不下。尤其是，基因 P53失活和EGFR/Akt过表达等修饰在高分化腺癌中频繁出现。 恶性卵巢癌。基因修饰会加剧炎症- 驱动趋化因子，可能加剧卵巢癌的发病机制。然而， 炎症驱动的趋化因子在慢性粒细胞白血病发病机制中的作用 人们对卵巢癌仍知之甚少。这项研究的长期目标是 确定趋化因子网络在卵巢癌发生中的具体作用。 靶向炎症驱动的趋化因子将有助于更好地理解 卵巢癌的发病机制，为卵巢癌的研究提供了重要的应用前景 趋化因子作为生物标志物和特异性趋化因子受体的潜在用途 抑制和抗炎药物在卵巢疾病防治中的应用 癌症。通过堵塞预防腹膜扩散和改善腹水 炎症驱动的趋化因子改善患者护理和妇女的总体存活率 与卵巢癌和其他肿瘤有关的炎症。

Project Summary/Abstract Ovarian cancer is the fifth leading cause of cancer deaths among women because this deadly insidious disease is typically asymptomatic until the malignancy has reached beyond the ovaries. Although the precise etiology remains unknown, the increasing evidence indicates ovarian cancer is one of inflammation-associated cancers derived from inflammatory diseases. Compared with normal ovarian epithelial cells, ovarian cancer cells expressed highly tumor necrosis factor-¿ (TNF) as a main proinflammatory cytokine that controls directly or indirectly chemokine networks. Growth-regulated oncogene (CXCL1) was significantly increased in ovarian cancer cells, and in the plasma and ascites of patients with ovarian cancer. Our recent studies have resulted that CXCL1, 2 and 8 are main inflammation-driven chemokines produced primarily and abundantly from ovarian cancer cells in response to inflammation. In other system, CXCL1 binds its specific receptor (CXCR2) and exert several functional roles such as cell proliferation, invasion, tumor formation and angiogenesis, which may be critical in the pathogenesis of ovarian cancer. These facts support that inflammation-driven chemokines promote ovarian cancer through inflammatory tumor microenvironments, which lead to massive ascites and widespread peritoneal dissemination as described in advanced ovarian cancer followed by the high mortality rate. In particular, genetic modifications such as p53 inactivity and EGFR/Akt overexpression are frequent in high- grade malignant ovarian cancer. The genetic modifications potentiate inflammation- driven chemokines, probably exacerbating the pathogenesis of ovarian cancer. However, the mechanisms inflammation-driven chemokines contribute to the pathogenesis of ovarian cancer are still poorly understood. The long-range goal of this research is to determine the specific contribution of chemokine networks to ovarian carcinogenesis. Targeting inflammation-driven chemokines will lead to a better understanding of the pathogenesis of ovarian cancer and provide important future applications for the potential use of chemokines as a biomarker and for use of specific chemokine receptor inhibitors and anti-inflammatory agents in the prevention and treatment of ovarian cancer. Preventing peritoneal dissemination and ameliorating ascites through blockage of inflammation-driven chemokines improve patient care and overall survival of women with ovarian cancer and other tumors related to inflammation.