title: Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.
abstract: 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.
authors.affiliation: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Duan
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Jingkun
authors.initials: J
authors.lastname: Qu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D049368:Receptors, Lysophosphatidic Acid / Q000032:analysis*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology* / Q000556:secondary
chemical_list: D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid