Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai, China.
J Exp Clin Cancer Res. 2010 Sep 10;29(1):124. doi: 10.1186/1756-9966-29-124.
Epithelial ovarian cancer is one of the most malignant cancers in women because metastasis occurs in the most of patients by the time of diagnosis. Cancer cells have strong capacity to form angiogenesis or vasculogenic mimicry, which plays the major role in its malignant phenotype. Vasculogenic mimicry might contribute to the failure of the angiogenesis-targeted therapy strategies. Under the microenvironment of the tumor, hypoxia is the most common phenomena because of the vast energy and oxygen consuming. In the present study, the endothelial-like cells induced by hypoxia from SKOV-3 and ES-2 ovarian cancer cells were harvested to investigate the changes in their biological behaviors.
The endothelial-like cells from SKOV-3 and ES-2 cells were harvested by laser capture microdissection. The biological behaviors of the endothelial-like cells, including proliferation, cell cycle, apoptosis, invasion and telomerase activity were determined by MTT, FCM, Transwell chamber and TRAP-ELISA methods. HIF-1α is the most important factor for the behavior changes under hypoxic condition. Some other genes relative to biological behaviors are also changes following the changes of HIF-1α. In order to elucidate the underlying mechanisms for these changes by hypoxia, the relative genes expressions including HIF-1α, CyclinD1, Flk-1, VEGF, p53 and V-src were determined by real-time PCR.
SKOV-3 and ES-2 cells were resistant to hypoxia by adoption of proliferation, apoptosis, differentiation and invasion. Combined with other studies, the more poorly cancer cells differentiate, the more strongly cells are resistant to hypoxia, the more possible to form vasculogenic mimicry. The changes in the expression of HIF-1α, and HIF-1α-dependent VEGF, Flk-1, Cyclin D1, and HIF-1α-independent p53 have been involved in this process.
HIF-1α took an important role in the behavioral changes of SKOV-3 and ES-2 cells by hypoxia. At the same time, other mechanisms were also involved in this process.
上皮性卵巢癌是女性最恶性的癌症之一，因为大多数患者在诊断时已经发生转移。癌细胞具有很强的形成血管生成或血管生成拟态的能力，这在其恶性表型中起着主要作用。血管生成拟态可能导致针对血管生成的治疗策略失败。在肿瘤的微环境下，由于大量的能量和氧气消耗，缺氧是最常见的现象。在本研究中，从 SKOV-3 和 ES-2 卵巢癌细胞中通过缺氧诱导内皮样细胞，以研究其生物学行为的变化。
通过激光捕获显微解剖法从 SKOV-3 和 ES-2 细胞中获取内皮样细胞。通过 MTT、FCM、Transwell 室和 TRAP-ELISA 方法测定内皮样细胞的生物学行为，包括增殖、细胞周期、凋亡、侵袭和端粒酶活性。HIF-1α 是缺氧条件下行为变化的最重要因素。其他一些与生物学行为相关的基因也随着 HIF-1α 的变化而变化。为了阐明缺氧引起这些变化的潜在机制，通过实时 PCR 测定了包括 HIF-1α、CyclinD1、Flk-1、VEGF、p53 和 V-src 在内的相关基因表达。
SKOV-3 和 ES-2 细胞通过增殖、凋亡、分化和侵袭对缺氧产生抗性。结合其他研究，癌细胞分化越差，对缺氧的抵抗力越强，形成血管生成拟态的可能性越大。HIF-1α 的表达变化以及 HIF-1α 依赖性的 VEGF、Flk-1、Cyclin D1 和 HIF-1α 非依赖性的 p53 的表达变化参与了这一过程。
HIF-1α 在 SKOV-3 和 ES-2 细胞通过缺氧引起的行为变化中起重要作用。同时，该过程还涉及其他机制。
