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Periostin contributes to the acquisition of multipotent stem cell-like properties in human mammary epithelial cells and breast cancer cells.

Wang X, Liu J, Wang Z, Huang Y, Liu W, Zhu X, Cai Y, Fang X, Lin S, Yuan L, Ouyang G - PLoS ONE (2013)

Bottom Line: Here we demonstrate that POSTN promotes a stem cell-like trait and a mesenchymal phenotype in human mammary epithelial cells and breast cancer cells.POSTN-overexpressing human mammary epithelial cells enhance breast tumor growth and metastasis.These data thus provide evidence of a new role for POSTN in mammary epithelial neoplasia and metastasis, suggesting that epithelial cancer cells might acquire CSC-like traits and a mesenchymal phenotype, as well as the multipotent potentials of MSCs to promote tumorigenesis and metastasis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.

ABSTRACT
Periostin (POSTN), a recently characterised matricellular protein, is frequently dysregulated in various malignant cancers and promotes tumor metastatic growth. POSTN plays a critical role in the crosstalk between murine breast cancer stem cells (CSCs) and their niche to permit metastatic colonization. However, whether pro-metastatic capability of POSTN is associated with multipotent potentials of mesenchymal stem cells (MSCs) has not been documented. Here we demonstrate that POSTN promotes a stem cell-like trait and a mesenchymal phenotype in human mammary epithelial cells and breast cancer cells. Interestingly, ectopic overexpression of POSTN or recombinant POSTN treatment can induce human mammary epithelial cells and breast cancer cells differentiation into multiple cell lineages that recapitulate part of the multilineage differentiation potentials of MSCs. Moreover, POSTN is highly expressed in bone marrow-derived MSCs and their derived adipocytes, chondrocytes, and osteoblasts in vitro. Furthermore, POSTN promotes the growth of xenograft tumors in vivo. POSTN-overexpressing human mammary epithelial cells enhance breast tumor growth and metastasis. These data thus provide evidence of a new role for POSTN in mammary epithelial neoplasia and metastasis, suggesting that epithelial cancer cells might acquire CSC-like traits and a mesenchymal phenotype, as well as the multipotent potentials of MSCs to promote tumorigenesis and metastasis. Therefore, targeting POSTN and other extracellular matrix components of tumor microenvironment may help to develop new therapeutical strategies to inhibit tumor metastasis.

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POSTN promotes a mesenchymal phenotype in MCF-10A and MCF-7 cells.A. POSTN-overexpressing cells exhibit a mesenchymal-like morphology. B. POSTN promotes cell invasion of human mammary epithelial cells and BCCs as detected by a matrigel-coated transwell invasion assay. C, D. Immunofluorescence analysis revealed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased. E, F. POSTN-expressing cells show increased levels of N-cadherin, fibrnectin, vimentin and α-SMA and decreased E-cadherin. Expression of epithelial and mesenchymal markers was analysed by western blotting.
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pone-0072962-g002: POSTN promotes a mesenchymal phenotype in MCF-10A and MCF-7 cells.A. POSTN-overexpressing cells exhibit a mesenchymal-like morphology. B. POSTN promotes cell invasion of human mammary epithelial cells and BCCs as detected by a matrigel-coated transwell invasion assay. C, D. Immunofluorescence analysis revealed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased. E, F. POSTN-expressing cells show increased levels of N-cadherin, fibrnectin, vimentin and α-SMA and decreased E-cadherin. Expression of epithelial and mesenchymal markers was analysed by western blotting.

Mentions: Recently, stem cell characteristics have been linked to the EMT program [25]. As shown in Figure 2A, compared with the vector-infected cells, POSTN-expressing MCF-10A and MCF-7 cells underwent a morphological change from a cobblestone-like epithelial morphology to an elongated fibroblast-like morphology. Enhanced cell invasion is a hallmark of EMT phenotype acquired by epithelial cells. We thus performed in vitro Matrigel transwell invasion assay to determine the effects of POSTN on cell invasion of MCF-10A and MCF-7 cells. Overexpression of POSTN results in a clear and potent invasive phenotype in both human mammary epithelial cells and BCCs in vitro (Figure 2B). Immunofluorescence analysis showed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased (Figure 2C, D). Western blotting analysis further confirmed that ectopic overexpression of POSTN resulted in down-regulation of epithelial marker E-cadherin and up-regulation of mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in human mammary epithelial cells and BCCs (Figure 2E, F). These data indicate that POSTN promotes a mesenchymal phenotype in human mammary epithelial cells and BCCs.


Periostin contributes to the acquisition of multipotent stem cell-like properties in human mammary epithelial cells and breast cancer cells.

Wang X, Liu J, Wang Z, Huang Y, Liu W, Zhu X, Cai Y, Fang X, Lin S, Yuan L, Ouyang G - PLoS ONE (2013)

POSTN promotes a mesenchymal phenotype in MCF-10A and MCF-7 cells.A. POSTN-overexpressing cells exhibit a mesenchymal-like morphology. B. POSTN promotes cell invasion of human mammary epithelial cells and BCCs as detected by a matrigel-coated transwell invasion assay. C, D. Immunofluorescence analysis revealed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased. E, F. POSTN-expressing cells show increased levels of N-cadherin, fibrnectin, vimentin and α-SMA and decreased E-cadherin. Expression of epithelial and mesenchymal markers was analysed by western blotting.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756944&req=5

pone-0072962-g002: POSTN promotes a mesenchymal phenotype in MCF-10A and MCF-7 cells.A. POSTN-overexpressing cells exhibit a mesenchymal-like morphology. B. POSTN promotes cell invasion of human mammary epithelial cells and BCCs as detected by a matrigel-coated transwell invasion assay. C, D. Immunofluorescence analysis revealed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased. E, F. POSTN-expressing cells show increased levels of N-cadherin, fibrnectin, vimentin and α-SMA and decreased E-cadherin. Expression of epithelial and mesenchymal markers was analysed by western blotting.
Mentions: Recently, stem cell characteristics have been linked to the EMT program [25]. As shown in Figure 2A, compared with the vector-infected cells, POSTN-expressing MCF-10A and MCF-7 cells underwent a morphological change from a cobblestone-like epithelial morphology to an elongated fibroblast-like morphology. Enhanced cell invasion is a hallmark of EMT phenotype acquired by epithelial cells. We thus performed in vitro Matrigel transwell invasion assay to determine the effects of POSTN on cell invasion of MCF-10A and MCF-7 cells. Overexpression of POSTN results in a clear and potent invasive phenotype in both human mammary epithelial cells and BCCs in vitro (Figure 2B). Immunofluorescence analysis showed that the mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in POSTN-expressing cells were increased while the epithelial marker E-cadherin was decreased (Figure 2C, D). Western blotting analysis further confirmed that ectopic overexpression of POSTN resulted in down-regulation of epithelial marker E-cadherin and up-regulation of mesenchymal markers N-cadherin, fibronectin, vimentin and α-SMA in human mammary epithelial cells and BCCs (Figure 2E, F). These data indicate that POSTN promotes a mesenchymal phenotype in human mammary epithelial cells and BCCs.

Bottom Line: Here we demonstrate that POSTN promotes a stem cell-like trait and a mesenchymal phenotype in human mammary epithelial cells and breast cancer cells.POSTN-overexpressing human mammary epithelial cells enhance breast tumor growth and metastasis.These data thus provide evidence of a new role for POSTN in mammary epithelial neoplasia and metastasis, suggesting that epithelial cancer cells might acquire CSC-like traits and a mesenchymal phenotype, as well as the multipotent potentials of MSCs to promote tumorigenesis and metastasis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.

ABSTRACT
Periostin (POSTN), a recently characterised matricellular protein, is frequently dysregulated in various malignant cancers and promotes tumor metastatic growth. POSTN plays a critical role in the crosstalk between murine breast cancer stem cells (CSCs) and their niche to permit metastatic colonization. However, whether pro-metastatic capability of POSTN is associated with multipotent potentials of mesenchymal stem cells (MSCs) has not been documented. Here we demonstrate that POSTN promotes a stem cell-like trait and a mesenchymal phenotype in human mammary epithelial cells and breast cancer cells. Interestingly, ectopic overexpression of POSTN or recombinant POSTN treatment can induce human mammary epithelial cells and breast cancer cells differentiation into multiple cell lineages that recapitulate part of the multilineage differentiation potentials of MSCs. Moreover, POSTN is highly expressed in bone marrow-derived MSCs and their derived adipocytes, chondrocytes, and osteoblasts in vitro. Furthermore, POSTN promotes the growth of xenograft tumors in vivo. POSTN-overexpressing human mammary epithelial cells enhance breast tumor growth and metastasis. These data thus provide evidence of a new role for POSTN in mammary epithelial neoplasia and metastasis, suggesting that epithelial cancer cells might acquire CSC-like traits and a mesenchymal phenotype, as well as the multipotent potentials of MSCs to promote tumorigenesis and metastasis. Therefore, targeting POSTN and other extracellular matrix components of tumor microenvironment may help to develop new therapeutical strategies to inhibit tumor metastasis.

Show MeSH
Related in: MedlinePlus