血管内皮生长因子与血小板源性生长因子在卵巢上皮性癌淋巴管形成中的作用

Roles of vascular endothelial growth factor and platelet-derived growth factor in lymphangiogenesis in epithelial ovarian carcinoma

目的探讨血管内皮生长因子（VEGF）和血小板源性生长因子（PDGF）在卵巢上皮性癌（卵巢癌）淋巴管形成中的作用。方法RT—PCR技术检测淋巴管内皮细胞核标志物Prox1和淋巴管形成相关因子VEGF—A、VEGF—C、VEGF-D及PDGF—A、PDGF—B、PDGF-C、PDGF—D在卵巢癌细胞株SKOV3、70例卵巢上皮性肿瘤（卵巢良性肿瘤15例、卵巢交界性肿瘤10例、卵巢癌45例）和20例正常卵巢组织中的表达情况。实时定量PCR技术检测上述90例卵巢组织中Prox1、VEGF-A、-C、-D及PDGF—A、-B、-C、-D的表达水平，并进行相关性分析。结果（1）Prox1在各种卵巢组织中均有表达，而在SKOV3细胞中无表达；VEGF-A、-C、-D及PDGF—A、-B、-C、-D在SKOV3细胞和各种卵巢组织中均有表达。（2）卵巢癌组织中Prox1（2．2±1．3）、VEGF—A（3．5±1．5）、VEGF—C（19±14）、VEGF—D（3．0±1．8）及PDGF—A（3．3±3．3）、PDGF—C（6．9±4．6）的表达水平高于卵巢良性肿瘤和交界性肿瘤（P均〈0．05）。（3）Prox1、VEGF—A和PDGF—A在卵巢癌Ⅲ～Ⅳ期（Prox1：2．6±1．3，VEGF—A：4．0±1．4，PDGF—A：4．1±3．7）、淋巴结转移阳性（Prox1：3．0±1．4，VEGF—A：4．1±1．7，PDGF—A：4．9±4．1）及腹膜转移阳性（Prox1：2．8±0．9，VEGF—A：4．0±1．8，PDGF—A：4．5±4．0）的组织中的表达水平，分别高于Ⅰ～Ⅱ期、淋巴结转移阴性和腹膜转移阴性者（P均〈0．05）；VEGF—C、VEGF-D在淋巴结转移阳性卵巢癌组织中的表达水平（VEGF—C：24±13，VEGF—D：3．9±2．0）高于淋巴结转移阴性者（P均〈0．05）。（4）卵巢癌组织中Prox1的表达水平与VEGF—D（r=0．62，P〈0．01）、PDGF-C（r=0．91，P〈0．01）、PDGF—D（r=0．61，P〈0．01）的表达水平呈正相关关系。结论VEGF—A、VEGF-C和PDGF—A可能通过参与淋巴管形成之外的机制促进卵巢癌的淋巴结转移；VEGF—D可以促进卵巢癌的淋巴管形成及淋巴结转移；PDGF—B与卵巢癌的淋巴管形成及淋巴结转移无关；PDGF—C、PDGF—D参与卵巢癌淋巴管形成，但无促进淋巴结转移的作用。

Objective To assess roles of vascular endothelial growth factor （VEGF） and plateletderived growth factor （PDGF） in the mechanisms of lymphangiogenesis in epithelial ovarian carcinoma. Methods （ 1 ） Expression of Prox1, a newly described lymphatic endothelial cell nucleus marker, VEGF- A, VEGF-C, VEGF-D and PDGF-A, PDGF-B, PDGF-C, PDGF-D were detected by RT-PCR in SKOV3 cell line and in 90 ovarian tissue samples, included 15 benign tumors, 10 borderline tumors, 45 malignant tumors and 20 normal ovarian samples. （2） Expression levels of Prox1 , VEGF-A, -C, -D and PDGF-A,-B, -C, -D were detected in 90 ovarian tissue sample mentioned above by real-time quantitative PCR （RTQ-PCR）. Results （1） Prox1 was expressed in ovarian samples mentioned above, while not detected in SKOV3 cell. VEGF-A, -C, -D and PDGF-A, -B, -C, -D were found in SKOV3 cell and various ovarian tissues. （2） Expression levels of Prox1 （2. 2 ± 1.3, P 〈0. 01 ）, VEGF-A （3.5 ± 1.5, P 〈0. 01 ）, VEGF- C （19±14, P〈0.01）, VEGF-D （3.0±1.8, P〈0.01） and PDGF-A （3.3±3.3, P〈0. 05）, PDGF-C （6. 9±4. 6, P 〈0. 01 ） in malignant group were found to be significantly higher than those in borderline group and benign group. （3） The expression levels of Proxl, VEGF-A and PDGF-A were significantly greater in samples from the patients with lymph node metastasis （ Prox1 ： 3.0 ± 1.4, VEGF-A ： 4. 1 ± 1.7, PDGF-A ： 4. 9 ± 4. 1 ）, peritoneum metastasis （ Prox1 ： 2. 8 ± 0. 9, VEGF-A ： 4. 0 ± 1.8, PDGF-A ： 4. 5 ± 4.0） and in stage Ⅲ -Ⅳ （Proxl： 2.6±1.3, VEGF-A： 4.0 ±1.4, PDGF-A： 4.1 ±3.7） than those without lymph node metastasis, without peritoneum metastasis and in stage Ⅰ - Ⅱ. There was a significant increased in the degree of VEGF-C and VEGF-D expression in positive lymph node metastasis group （ VEGF- C： 24 -± 13, VEGF-D： 3.9 ±2. 0） compared with negative group （P 〈0. 05）. （4） There were significant positive correlations between the expression levels of Proxl and VEGF-D （ r = 0. 62, P 〈 0. 01 ） , PDGF-C （r=0.91, P〈0.01） orPDGF-D （r=0.61, P〈0.01）. Conclusions VEGF-A, VEGF-C and PDGF-A may promote lymphatic metastasis in epithelial ovarian carcinoma through else mechanisms other than lymphangiogenesis. VEGF-D may facilitate lymphangiogenesis and lymph node metastasis in epithelial ovarian cancer. There is no significant correlation between the expression of PDGF-B and lymphangiogenesis and lymph node metastasis. PCGF-C and PDGF-D may motivate lymphangiogenesis, but could not participate in lymph node metastasis in ovarian carcinoma.