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血小板衍生生长因子-D通过调节基质金属蛋白酶2和9促进卵巢癌侵袭。

Platelet-derived growth factor-D promotes ovarian cancer invasion by regulating matrix metalloproteinases 2 and 9.

作者信息

Wang Yuan, Hu Chaoying, Dong Ruofan, Huang Xiaoyan, Qiu Haifeng

机构信息

Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Soochow University, Wuxi, China.

出版信息

Asian Pac J Cancer Prev. 2011;12(12):3367-70.

Abstract

OBJECTIVE

Platelet-derived growth factor-D (PDGF-D) can enhance invasion and metastasis in several human malignancies, though little is known about its functions in ovarian cancer.

METHODS

In this study, we detected expression of PDGF-D in ovarian cancer tissues and cell lines by qRT-PCR, immunohistochemistry and western blotting, investigating the influences on cellular proliferation, invasion and apoptosis by upregulating its expression.

RESULTS

79.5% (62/78) of ovarian cancer samples proved to be PDGF-D positive, in contrast to just 38.5%(30/78) in their adjacent non-cancer tissues (p<0.001). Moreover, we found high levels of PDGF-D were correlated with lymph node metastasis (p=0.025) and positive cancer cells in abdominal washings/ascites (p=0.042). In vitro, upregulation of PDGF-D enhanced the invasiveness of SKOV3 cells (p<0.01), but had no impact on cellular proliferation or apoptosis. Furthermore, expression of matrix metalloproteinases 2/9 (MMP2 and MMP9) was positively related with PDGF-D, indicating their involvement in the invasion and metastasis of ovarian cancer.

CONCLUSIONS

Our findings proved that PDGF-D could promote ovarian cancer invasion by upregulating MMPs, which might be a potential target for ovarian cancer treatment.

摘要

目的

血小板衍生生长因子-D(PDGF-D)可增强多种人类恶性肿瘤的侵袭和转移能力,不过其在卵巢癌中的功能鲜为人知。

方法

在本研究中,我们通过qRT-PCR、免疫组织化学和蛋白质印迹法检测了卵巢癌组织和细胞系中PDGF-D的表达,通过上调其表达来研究对细胞增殖、侵袭和凋亡的影响。

结果

79.5%(62/78)的卵巢癌样本被证明为PDGF-D阳性,相比之下,其相邻非癌组织中这一比例仅为38.5%(30/78)(p<0.001)。此外,我们发现高水平的PDGF-D与淋巴结转移(p=0.025)以及腹水中癌细胞阳性(p=0.042)相关。在体外,上调PDGF-D可增强SKOV3细胞的侵袭能力(p<0.01),但对细胞增殖或凋亡无影响。此外,基质金属蛋白酶2/9(MMP2和MMP9)的表达与PDGF-D呈正相关,表明它们参与了卵巢癌的侵袭和转移。

结论

我们的研究结果证明,PDGF-D可通过上调基质金属蛋白酶促进卵巢癌侵袭,这可能是卵巢癌治疗的一个潜在靶点。

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