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 LPA2 and LPA3 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 LPA2 and LPA3
protein was also consistently observed in
carcinomas. The LPA3 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 LPA3 expression compared with
luminal-type A and B breast
cancers. Suppression of LPA3 by
shRNA did not influence cell growth in
breast cancer cells. However, the migration and invasion of TNBC cells were significantly inhibited by LPA3-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 LPA3 is a potential therapeutic target for the treatment of TNBCs.