Lysophosphatidic acid receptor 2/3‐mediated IL‐8‐dependent angiogenesis in cervical cancer cells

• DOI: 10.1002/ijc.26476
• Publication Date: 2011-09-30T17:58:33Z
• Authors: Ruey‐Jien Chen; Shee‐Uan Chen; Chia‐Hung Chou; Ming‐Chieh Lin
• Keywords: Receptor expression

The expression of lysophosphatidic acid (LPA)-specific receptors in cervical cancer has not been clearly defined. In this study, we identified LPA1, LPA2 and LPA3 receptors' mRNA SiHa, HeLa CaSki cell lines by RT-PCR. These were associated with tumor proliferation vitro. We then used a xenograph animal model to evaluate the effects these on vivo tumorigenicity. When SiHa cells different receptor patterns seeded backs SCID mice, resulting knockout both significantly attenuated growth; decrease growth was found be linked decreased angiogenesis (microvessel density), suggesting that are crucial for through an angiogenic mechanism. further investigated mechanism LPA 2/3-mediated capability analyzing factors protein lysates from tumors, detecting interleukin (IL-8) after treating siRNA, evaluating biological role LPA-enhanced IL-8 via endothelial tube formation, monolayer permeability, migration assays, xenograft mice modeling. is mediated IL-8. Finally, evaluated regulation pathways involved LPA-induced expression. occurs Gi/PI3K/AKT, Gi/PKC IκB/NF-κB signaling. conclusion, propose might play important IL-8-dependent angiogenesis.