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

Sun K, Cai H, Duan X, Yang Y, Li M, Qu J, Zhang X, Wang J - Clin. Exp. Med. (2014)

Bottom Line: 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).The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Inactivated LPA3 by Ki16425 suppressed migration and invasion of TNBC cells. a MDA-MB-231 cells were treated with indicated concentrations of Ki16428 for 1 h, and then cell viability was measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. b, c Migration (b) and invasion (c) of MDA-MB-231 cells were inhibited by ki16425. MDA-MB-231 cells were pretreated with indicated concentrations of ki16425 for 1 h and then transferred to collagen- or matrigel-coated transwell chambers for migration and invasion experiments, respectively. *P < 0.05; **P < 0.01; ***P < 0.001
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Fig5: Inactivated LPA3 by Ki16425 suppressed migration and invasion of TNBC cells. a MDA-MB-231 cells were treated with indicated concentrations of Ki16428 for 1 h, and then cell viability was measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. b, c Migration (b) and invasion (c) of MDA-MB-231 cells were inhibited by ki16425. MDA-MB-231 cells were pretreated with indicated concentrations of ki16425 for 1 h and then transferred to collagen- or matrigel-coated transwell chambers for migration and invasion experiments, respectively. *P < 0.05; **P < 0.01; ***P < 0.001

Mentions: We used Ki16425, an antagonist for LPA1 and LPA3, to confirm the critical roles of LPA3 in TNBC cells. We first showed that pre-treating MDA-MB-231 cells with Ki16425 did not influence cell viability (Fig. 5a). We then evaluated the effects of Ki16425 on migration and invasion of TNBC cells, using transwell assays. As shown in Fig. 5b, c, Ki16425 suppressed migration and invasion of MDA-MB-231 cells in a dose-dependent manner.Fig. 5


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

Sun K, Cai H, Duan X, Yang Y, Li M, Qu J, Zhang X, Wang J - Clin. Exp. Med. (2014)

Inactivated LPA3 by Ki16425 suppressed migration and invasion of TNBC cells. a MDA-MB-231 cells were treated with indicated concentrations of Ki16428 for 1 h, and then cell viability was measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. b, c Migration (b) and invasion (c) of MDA-MB-231 cells were inhibited by ki16425. MDA-MB-231 cells were pretreated with indicated concentrations of ki16425 for 1 h and then transferred to collagen- or matrigel-coated transwell chambers for migration and invasion experiments, respectively. *P < 0.05; **P < 0.01; ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4522273&req=5

Fig5: Inactivated LPA3 by Ki16425 suppressed migration and invasion of TNBC cells. a MDA-MB-231 cells were treated with indicated concentrations of Ki16428 for 1 h, and then cell viability was measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. b, c Migration (b) and invasion (c) of MDA-MB-231 cells were inhibited by ki16425. MDA-MB-231 cells were pretreated with indicated concentrations of ki16425 for 1 h and then transferred to collagen- or matrigel-coated transwell chambers for migration and invasion experiments, respectively. *P < 0.05; **P < 0.01; ***P < 0.001
Mentions: We used Ki16425, an antagonist for LPA1 and LPA3, to confirm the critical roles of LPA3 in TNBC cells. We first showed that pre-treating MDA-MB-231 cells with Ki16425 did not influence cell viability (Fig. 5a). We then evaluated the effects of Ki16425 on migration and invasion of TNBC cells, using transwell assays. As shown in Fig. 5b, c, Ki16425 suppressed migration and invasion of MDA-MB-231 cells in a dose-dependent manner.Fig. 5

Bottom Line: 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).The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus