Cells that expressed LPA2 or LPA3 spread to more tissues than cells expressing LPA1, according to JNCI paper.
Researchers at the University of Texas M. D. Anderson Cancer Center in Houston believe that they have found evidence that lysophosphatidic acid (LPA) receptor expression and LPA signaling regulate the behavior and aggressiveness of ovarian cancer cells. They add that the overexpression of the LPA2 or LPA3 receptor likely plays a role in the progression of the disease.
Previous studies indicated that LPA is present at high levels in ascites fluid in ovarian cancer patients. Research also showed that the receptors are expressed in several malignancies including ovarian cancers.
The team thus engineered human ovarian cancer cells to overexpress or prohibit each LPA receptors (LPA1, LPA2, or LPA3) to determine whether LPA and its receptors directly contribute to the oncogenic phenotype in ovarian tumors. They assayed cell behavior in vitro and by injecting them into xenograft mouse models and compared results to control cells that do not express the receptors.
The scientists found that LPA2 and LPA3 did form tumors that are bigger and more aggressive. Ovarian cancer cells that expressed the LPA receptors produced a larger volume of ascites than cells that did not express the receptors. Additionally, the LPA receptor-expressing cells invaded the peritoneal cavity in more than 75% of the animals. Injection of ovarian cancer cells expressing any one of the three LPA receptors into mice led to metastatic tumors. However, the cells that expressed LPA2 or LPA3 metastasized to a wider array of tissues than did the cells expressing LPA1.
The paper appears in the November 11 edition of the Journal of the National Cancer Institute.