SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma

  • Authors:
    • Fenghui Peng
    • Yanping Zhong
    • Yunfeng Liu
    • Yueming Zhang
    • Yihong Xie
    • Yingxin Lu
    • Xinyin Zhang
    • Danrong Li
  • View Affiliations

  • Published online on: October 19, 2017     https://doi.org/10.3892/ijo.2017.4168
  • Pages:1920-1928
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Abstract

Lymph node metastasis is one of the most valuable determinants for the prognosis of ovarian cancer. However, the molecular mechanisms underlying lymphangiogenesis in ovarian cancer is still poorly understood. Secreted protein acidic and rich in cysteine (SPARC), a Ca2+-binding matricellular glycoprotein that modulates cell adhesion, migration and differentiation, is thought to play a decisive role in tumor metastasis. Vascular endothelial growth factor (VEGF)-C and VEGF-D contributes to tumor-associated lymphatic vessel growth, enhancing the metastatic spread of tumor cells to lymph nodes. The aim of the present study was to investigate the relationship among SPARC, VEGFs and lymph node metastasis in ovarian cancer. We found that SKOV3 cells expressed high-level SPARC, much more than SKOV3-PM4 cells (a subline with high directional lymphatic metastatic potentials established from the metastatic lymph node generated by human ovarian carcinoma cell line SKOV3 in nude mice) did at both mRNA and protein levels. A SPARC-overexpressed SKOV3-PM4 cell line was constructed and it was found that upregulation of SPARC expression suppressed the growth, migration and invasion of SKOV3-PM4 cells as well as markedly reduced the expression of VEGF-D at both mRNA and protein level by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. In 47 of ovarian malignant tissues, the expression of SPARC, VEGF-C and VEGF-D were determined by immunohistochemistry. Lymphatic microvessel density (LVD) and microvessel density (MVD) were evaluated by immunostaining with CD34 and D2-40 antibodies, respectively. We found that SPARC expression was significantly lower in tissues with lymph node metastasis as compared to tissues without lymph node metastasis. SPARC expression was inversely associated with the degree of malignancy and it had a negative correlation with VEGF-C expression, VEGF-D expression, LVD and MVD which were actually higher for advanced tumors than for non-advanced tumors. These results suggest SPARC might function as a tumor suppressor inhibiting angiogenesis and lymphangiogenesis in ovarian cancer by reducing the expression of VEGF-C and VEGF-D.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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Copy and paste a formatted citation
APA
Peng, F., Zhong, Y., Liu, Y., Zhang, Y., Xie, Y., Lu, Y. ... Li, D. (2017). SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma. International Journal of Oncology, 51, 1920-1928. https://doi.org/10.3892/ijo.2017.4168
MLA
Peng, F., Zhong, Y., Liu, Y., Zhang, Y., Xie, Y., Lu, Y., Zhang, X., Li, D."SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma". International Journal of Oncology 51.6 (2017): 1920-1928.
Chicago
Peng, F., Zhong, Y., Liu, Y., Zhang, Y., Xie, Y., Lu, Y., Zhang, X., Li, D."SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma". International Journal of Oncology 51, no. 6 (2017): 1920-1928. https://doi.org/10.3892/ijo.2017.4168