Platelet-activating factor and metastasis: Calcium-independent phospholipase a2β deficiency protects against breast cancer metastasis to the lung

Jane Mchowat, Gail Gullickson, Richard G. Hoover, Janhavi Sharma, John Turk, Jacki Kornbluth

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We determined the contribution of calcium-independent phospholipase A 2β (iPLA 2β) to lung metastasis development following breast cancer injection into wild-type (WT) and iPLA 2β-knockout (iPLA 2β-KO) mice. WT and iPLA 2β-KO mice were injected in the mammary pad with 200,000 E0771 breast cancer cells. There was no difference in primary tumor size between WT and iPLA 2β-KO mice at 27 days postinjection. However, we observed an 11-fold greater number of breast cancer cells in the lungs of WT mice compared with iPLA 2β-KO animals (P < 0.05). Isolated WT lung endothelial cells demonstrated a significant increase in plateletactivating factor (PAF) production when stimulated with thrombin [1 IU/ml, 10 min, 4,330 ± 555 vs. 15,227 ± 1,043 disintegrations per minute (dpm), P < 0.01] or TNF-α (10 ng/ml, 2 h, 16,532 ± 538 dpm, P < 0.01). Adherence of E0771 cells to WT endothelial cells was increased by thrombin (4.8 ± 0.3% vs. 70.9 ± 6.3, P < 0.01) or TNF-α (60.5 ± 4.3, P < 0.01). These responses were blocked by pretreatment with the iPLA 2β-selective inhibitor (S)-bromoenol lactone and absent in lung endothelial cells from iPLA 2β-KO mice. These data indicate that endothelial cell iPLA 2β is responsible for PAF production and adherence of E0771 cells and may play a role in cancer cell migration to distal locations.

Original languageEnglish
Pages (from-to)C825-C832
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Bromoenol lactone
  • Endothelium
  • Inflammation

Fingerprint Dive into the research topics of 'Platelet-activating factor and metastasis: Calcium-independent phospholipase a2β deficiency protects against breast cancer metastasis to the lung'. Together they form a unique fingerprint.

  • Cite this