Limits...
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.

Show MeSH

Related in: MedlinePlus

POSTN induces adipogenic and chondrogenic differentiation.A. Following adipogenic differentiation, MCF-10A/POSTN, MCF-7/POSTN cells and hMSCs stained positive with oil red O (top) and fluorescent LipidTox, which stains oil droplets (bottom). B, C. Real-time RT-PCR analysis for the expression of the adipocyte markers PPARγand ADFP in MCF-10A and MCF-7 cells and their POSTN-overexpressing cells subjected to adipocyte differentiation for 21 days. The data are means ± SD. *P<0.05, **P<0.01. D. Chondrocytic nodules formed by MCF-10A/POSTN cells and hMSCs stained positive with alcian blue 8 GX (left panel). Immunohistochemistry was performed on chondrocyte sections using antibody against collagen II (right panel). MCF-10A/Vector cells, MCF-7/Vector and MCF-7/POSTN cells did not form any chondrocytic nodules under identical conditions.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756944&req=5

pone-0072962-g003: POSTN induces adipogenic and chondrogenic differentiation.A. Following adipogenic differentiation, MCF-10A/POSTN, MCF-7/POSTN cells and hMSCs stained positive with oil red O (top) and fluorescent LipidTox, which stains oil droplets (bottom). B, C. Real-time RT-PCR analysis for the expression of the adipocyte markers PPARγand ADFP in MCF-10A and MCF-7 cells and their POSTN-overexpressing cells subjected to adipocyte differentiation for 21 days. The data are means ± SD. *P<0.05, **P<0.01. D. Chondrocytic nodules formed by MCF-10A/POSTN cells and hMSCs stained positive with alcian blue 8 GX (left panel). Immunohistochemistry was performed on chondrocyte sections using antibody against collagen II (right panel). MCF-10A/Vector cells, MCF-7/Vector and MCF-7/POSTN cells did not form any chondrocytic nodules under identical conditions.

Mentions: To explore whether the mesenchymal-like cells induced by ectopic POSTN expression exhibit the multilineage differentiation potential of MSCs, we further characterised the MSC traits of MCF-10A/POSTN cells. We found that MCF-10A/POSTN cells exhibited the typical developmental potential of MSCs to differentiate into oil red O-positive and fluorescent LipidTox-positive adipocytes, alcian blue-positive chondrocytes, and alizarin red S-positive and von Kossa-positive mature osteoblasts when cultured in the appropriate differentiation conditions (Figure 3A, 3D, 4A, 4B). Real-time RT-PCR analysis showed that the adipocyte markers PPARγand ADFP (Figure 3B, C) and the osteoblast markers BSP and Runx2 (Figure 4C, D) are markedly upregulated in MCF-10A/POSTN cells grown under adipogenic or osteogenic differentiation conditions for 21 days, but not in MCF-10A/Vector cells. MCF-10A/POSTN cells can form chondrocytic nodules that are positive for collagen II, whereas MCF-10A/Vector cells did not form any chondrocyte nodules under identical conditions (Figure 3D). Moreover, MCF-10A/POSTN cells can differentiate into a CD56-positive myogenic lineage with increased expression of the myogenic markers MyoG and Pax3 under myogenic differentiation culture for 4 weeks, but not the vector cells (Figure 4E, F). We further demonstrate that POSTN endows MCF-7 cells with the potential to differentiate into adipocytes and osteoblasts (Figure 3A, 4A, 4B), but not into chondrogenic and myogenic lineages (data not shown). Real-time RT-PCR analysis also showed that the adipocyte markers ADFP (Figure 3C) and the osteoblast markers Runx2 (Figure 4D) are markedly upregulated in MCF-7/POSTN cells grown under adipogenic or osteogenic differentiation conditions for 21 days when compared with MCF-7/Vector control cells. We further confirmed these results by treating human mammary epithelial cells and BCCs with human recombinant POSTN protein (Figure 5A, B, C). These observations indicate that POSTN promotes MCF-10A and MCF-7 cells to exhibit multilineage differentiation potentials, in part, similar to MSCs.


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 induces adipogenic and chondrogenic differentiation.A. Following adipogenic differentiation, MCF-10A/POSTN, MCF-7/POSTN cells and hMSCs stained positive with oil red O (top) and fluorescent LipidTox, which stains oil droplets (bottom). B, C. Real-time RT-PCR analysis for the expression of the adipocyte markers PPARγand ADFP in MCF-10A and MCF-7 cells and their POSTN-overexpressing cells subjected to adipocyte differentiation for 21 days. The data are means ± SD. *P<0.05, **P<0.01. D. Chondrocytic nodules formed by MCF-10A/POSTN cells and hMSCs stained positive with alcian blue 8 GX (left panel). Immunohistochemistry was performed on chondrocyte sections using antibody against collagen II (right panel). MCF-10A/Vector cells, MCF-7/Vector and MCF-7/POSTN cells did not form any chondrocytic nodules under identical conditions.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0072962-g003: POSTN induces adipogenic and chondrogenic differentiation.A. Following adipogenic differentiation, MCF-10A/POSTN, MCF-7/POSTN cells and hMSCs stained positive with oil red O (top) and fluorescent LipidTox, which stains oil droplets (bottom). B, C. Real-time RT-PCR analysis for the expression of the adipocyte markers PPARγand ADFP in MCF-10A and MCF-7 cells and their POSTN-overexpressing cells subjected to adipocyte differentiation for 21 days. The data are means ± SD. *P<0.05, **P<0.01. D. Chondrocytic nodules formed by MCF-10A/POSTN cells and hMSCs stained positive with alcian blue 8 GX (left panel). Immunohistochemistry was performed on chondrocyte sections using antibody against collagen II (right panel). MCF-10A/Vector cells, MCF-7/Vector and MCF-7/POSTN cells did not form any chondrocytic nodules under identical conditions.
Mentions: To explore whether the mesenchymal-like cells induced by ectopic POSTN expression exhibit the multilineage differentiation potential of MSCs, we further characterised the MSC traits of MCF-10A/POSTN cells. We found that MCF-10A/POSTN cells exhibited the typical developmental potential of MSCs to differentiate into oil red O-positive and fluorescent LipidTox-positive adipocytes, alcian blue-positive chondrocytes, and alizarin red S-positive and von Kossa-positive mature osteoblasts when cultured in the appropriate differentiation conditions (Figure 3A, 3D, 4A, 4B). Real-time RT-PCR analysis showed that the adipocyte markers PPARγand ADFP (Figure 3B, C) and the osteoblast markers BSP and Runx2 (Figure 4C, D) are markedly upregulated in MCF-10A/POSTN cells grown under adipogenic or osteogenic differentiation conditions for 21 days, but not in MCF-10A/Vector cells. MCF-10A/POSTN cells can form chondrocytic nodules that are positive for collagen II, whereas MCF-10A/Vector cells did not form any chondrocyte nodules under identical conditions (Figure 3D). Moreover, MCF-10A/POSTN cells can differentiate into a CD56-positive myogenic lineage with increased expression of the myogenic markers MyoG and Pax3 under myogenic differentiation culture for 4 weeks, but not the vector cells (Figure 4E, F). We further demonstrate that POSTN endows MCF-7 cells with the potential to differentiate into adipocytes and osteoblasts (Figure 3A, 4A, 4B), but not into chondrogenic and myogenic lineages (data not shown). Real-time RT-PCR analysis also showed that the adipocyte markers ADFP (Figure 3C) and the osteoblast markers Runx2 (Figure 4D) are markedly upregulated in MCF-7/POSTN cells grown under adipogenic or osteogenic differentiation conditions for 21 days when compared with MCF-7/Vector control cells. We further confirmed these results by treating human mammary epithelial cells and BCCs with human recombinant POSTN protein (Figure 5A, B, C). These observations indicate that POSTN promotes MCF-10A and MCF-7 cells to exhibit multilineage differentiation potentials, in part, similar to MSCs.

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