Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers

Triple receptor-negative breast cancers (TNBCs) generally have poor prognoses because of the loss of therapeutic targets. As lysophosphatidic acid (LPA) receptor signaling has been shown to affect breast cancer initiation and progression, we try to evaluate the potential roles of LPA receptors in TNBCs. We examined mRNA and protein expressions of LPA receptors 1-3, using quantitative real-time PCR and immunohistochemical analyses in normal (n = 37), benign disease (n = 55), and breast cancer tissues (n = 82). Carcinomas expressed higher levels of LPA(2) and LPA(3) mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively). Enhanced immunohistochemical staining for LPA(2) and LPA(3) protein was also consistently observed in carcinomas. The LPA(3) overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression. TNBC tissues and cell lines showed the highest LPA(3) expression compared with luminal-type A and B breast cancers. Suppression of LPA(3) by shRNA did not influence cell growth in breast cancer cells. However, the migration and invasion of TNBC cells were significantly inhibited by LPA(3)-shRNA or inhibitor, which had no or less effect on normal and non-TNBC breast cells. In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA(3) is a potential therapeutic target for the treatment of TNBCs.