Angiogenic effect of lysophosphatidic acid receptors on cervical cancer cells

Cervical cancer was recently reported to be the fourth leading cause of cancer death in women worldwide, causing an estimated 265,700 deaths a year. This malignancy is typically treated by radical surgery during the disease’s early stages, by radiotherapy combined with chemotherapy for locally advanced cases, and by chemotherapy for metastatic or recurrent cases. For advanced cases, development of targeted therapies to supplement traditional treatments may contribute to the interference of tumor growth and invasion and to the improvement of patient survival. Since angiogenesis plays an important role in the progression of cervical cancer, angiogenic factors are potential targets. Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are the two most potent angiogenic factors. Adding bevacizumab, a recombinant humanized monoclonal antibody and VEGF antagonist, to chemotherapy regimens for recurrent cervical cancer has been shown to prolong median overall survival (OS) by 3.7 months. Lysophosphatidic acid (LPA), a naturally occurring lipid and autotaxin (ATX), is a major LPA-producing enzyme. In cervical cancer cells, LPA may activate LPA receptors LPA2 and LPA3 and play an important role in tumor growth through IL-8-dependent angiogenesis. The usefulness of a molecular therapy which targets the ATX-LPA-IL-8 cascade for the treatment of advanced cervical cancer merits further investigation.