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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

Inhibition of LPA3 decreased migration and invasion of TNBC cells. a Expression of LPA3 was decreased by shRNA. MCF-10A, MCF-7, and MDA-MB-231 cells were transfected with control and LPA3 shRNA. Forty-eight hours later, cell lysates were analyzed by Western blots with anti-LPA3 antibody. b The effect of LPA3 on breast cancer cells growth, as measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. c, d Cell transwell assays were conducted to investigate the role of LPA3 on breast cancer cells migration (c) and invasion (d). The results are presented as the mean ± SD of cell number obtained in three independent experiments. **P < 0.01; ***P < 0.001
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Fig4: Inhibition of LPA3 decreased migration and invasion of TNBC cells. a Expression of LPA3 was decreased by shRNA. MCF-10A, MCF-7, and MDA-MB-231 cells were transfected with control and LPA3 shRNA. Forty-eight hours later, cell lysates were analyzed by Western blots with anti-LPA3 antibody. b The effect of LPA3 on breast cancer cells growth, as measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. c, d Cell transwell assays were conducted to investigate the role of LPA3 on breast cancer cells migration (c) and invasion (d). The results are presented as the mean ± SD of cell number obtained in three independent experiments. **P < 0.01; ***P < 0.001

Mentions: To further analyze the role of LPA3 in breast tumorigenesis, we conducted cell proliferation, migration, and invasion assays of LPA3- and control-shRNA-transfected breast epithelial cells, including normal immortal cells MCF-10A, luminal cells MCF-7, and TNBC cells MDA-MB-231. LPA3 was effectively down-regulated by shRNA in all three cell lines (Fig. 4a). Cell proliferation tested by MTT showed that suppression of LPA3 did not influence cell growth in all three cell lines (Fig. 4b). However, cells with LPA3-shRNA migrated significantly less than controls in MDA-MB-231 cells (Fig. 4c). Although LPA3-shRNA also reduced migration of MCF-7 cells, the inhibitory capacity was weaker than in MDA-MB-231 cells (Fig. 4c). We also assessed the effect of LPA3 knockdown on cellular invasion and revealed LPA3 loss significantly decreased invasion of MDA-MB-231 cells, but had less or no effect on MCF-10A and MCF-7 cells (Fig. 4d).Fig. 4


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)

Inhibition of LPA3 decreased migration and invasion of TNBC cells. a Expression of LPA3 was decreased by shRNA. MCF-10A, MCF-7, and MDA-MB-231 cells were transfected with control and LPA3 shRNA. Forty-eight hours later, cell lysates were analyzed by Western blots with anti-LPA3 antibody. b The effect of LPA3 on breast cancer cells growth, as measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. c, d Cell transwell assays were conducted to investigate the role of LPA3 on breast cancer cells migration (c) and invasion (d). The results are presented as the mean ± SD of cell number obtained in three independent experiments. **P < 0.01; ***P < 0.001
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Related In: Results  -  Collection

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Fig4: Inhibition of LPA3 decreased migration and invasion of TNBC cells. a Expression of LPA3 was decreased by shRNA. MCF-10A, MCF-7, and MDA-MB-231 cells were transfected with control and LPA3 shRNA. Forty-eight hours later, cell lysates were analyzed by Western blots with anti-LPA3 antibody. b The effect of LPA3 on breast cancer cells growth, as measured using the MTT assay. The results are presented as the mean ± SD of fold increased to initiation obtained in 3 independent experiments. c, d Cell transwell assays were conducted to investigate the role of LPA3 on breast cancer cells migration (c) and invasion (d). The results are presented as the mean ± SD of cell number obtained in three independent experiments. **P < 0.01; ***P < 0.001
Mentions: To further analyze the role of LPA3 in breast tumorigenesis, we conducted cell proliferation, migration, and invasion assays of LPA3- and control-shRNA-transfected breast epithelial cells, including normal immortal cells MCF-10A, luminal cells MCF-7, and TNBC cells MDA-MB-231. LPA3 was effectively down-regulated by shRNA in all three cell lines (Fig. 4a). Cell proliferation tested by MTT showed that suppression of LPA3 did not influence cell growth in all three cell lines (Fig. 4b). However, cells with LPA3-shRNA migrated significantly less than controls in MDA-MB-231 cells (Fig. 4c). Although LPA3-shRNA also reduced migration of MCF-7 cells, the inhibitory capacity was weaker than in MDA-MB-231 cells (Fig. 4c). We also assessed the effect of LPA3 knockdown on cellular invasion and revealed LPA3 loss significantly decreased invasion of MDA-MB-231 cells, but had less or no effect on MCF-10A and MCF-7 cells (Fig. 4d).Fig. 4

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