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

OBJECTIVE

To assess roles of vascular endothelial growth factor (VEGF) and platelet-derived 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 Prox1, 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 (Prox1: 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 Prox1 and VEGF-D (r = 0.62, P < 0.01), PDGF-C (r = 0.91, P < 0.01) or PDGF-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.