Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment
Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment
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DOI：
10.1002/cbin.10131
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发表时间：
2013-10
影响因子：
3.9
通讯作者：
Hong Yang;W. Zou;Biliang Chen
中科院分区：
文献类型：
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作者：
Hong Yang;W. Zou;Biliang Chen
卵巢癌是一种以活化侵袭、远处转移、抗癌药物耐药、血管生成和代谢为特征的致命性恶性肿瘤。CD147是一种细胞外基质金属蛋白酶诱导剂，在大多数卵巢肿瘤中高表达，在卵巢癌等恶性肿瘤的发生发展中起重要作用。然而，引发这种过度表达的因素(S)尚不清楚。由于肿瘤的快速繁殖和低氧微环境，肿瘤以糖酵解为能量来源，产生的乳酸对细胞有害。为了生存，过量的乳酸需要通过单羧酸转运体(MCT)运输。MCT1和MCT4的功能需要CD147的辅助。CD147基因的3‘侧翼有两个低氧诱导因子结合位点。低氧微环境是CD147过度表达的主要启动者，从而赋予卵巢癌恶性特性，这是合乎逻辑的假设。为了验证这一假说，需要一个能够代表自发性卵巢癌的模型。
Ovarian cancer is a lethal malignant tumour characterised by activated invasion, distant metastasis, anti‐cancer drug resistance, angiogenesis and metabolism. CD147, an extracellular matrix metalloproteinase inducer, is overexpressed in most ovarian tumours and plays an important role in the progression of ovarian cancer and other malignant tumours. However, the factor(s) initiating this overexpression is unknown. Because of rapid reproduction and their hypoxic microenvironment, malignant tumours use glycolysis for energy, and lactic acid produced is harmful to the cells. For survival, excessive lactate needs to be transported by monocarboxylate transporters (MCTs). Functioning of MCT1 and MCT4 require the ancillary of CD147. The gene for CD147 possesses two hypoxia‐inducible factors binding sites in its 3′‐flank. It is logical to postulate that the hypoxic microenvironment is a major initiator of the overexpression of CD147, thus conferring on ovarian cancers their malignant properties. A model that can represent spontaneous ovarian cancer is necessary to verify this hypothesis.