[The effect of cyclooxygenase-2 on lymphangiogenesis in breast cancer]

Zhonghua Wai Ke Za Zhi. 2008 Jan 15;46(2):132-5.
[Article in Chinese]

Abstract

Objective: To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer.

Methods: By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examined in the tissue samples of primary tumors from 94 patients underwent surgical resections for breast cancer from November 1998 to March 2002. Eighty-three patients were followed-up. The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses. The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2 (1 microg/ml) and Trastuzumab (1 microg/ml), respectively.

Results: COX-2 over-expression was observed in 46.8% of surgical specimens (44/94), while VEGF-C overexpression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression (P < 0.01), micro-lymphatic vessels (P = 0.032) and metastatic lymph nodes (P = 0. 035). Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did, including disease-free survival (P = 0.010) and overall survival (P = 0.040). Nimesulide could down-regulate the expressions of VEGF-C mRNA and protein in a does-dependent manner, while PGE2 could up-regulate the expressions. The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab.

Conclusions: COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymph-angiogenic pathway, then affect the prognosis of the patients with breast cancer.

Publication types

  • English Abstract

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 / physiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphangiogenesis
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Vascular Endothelial Growth Factor C
  • Cyclooxygenase 2
  • PTGS2 protein, human