Periostin contributes to the acquisition of multipotent stem cell-like properties in human mammary epithelial cells and breast cancer cells.
Periostin contributes to the acquisition of multipotent stem cell-like properties in human mammary epithelial cells and breast cancer cells.
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Periostin 有助于获得人类乳腺上皮细胞和乳腺癌细胞的多能干细胞样特性
DOI：
10.1371/journal.pone.0072962
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ouyang G
中科院分区：
文献类型：
--
作者：
Wang X;Liu J;Wang Z;Huang Y;Liu W;Zhu X;Cai Y;Fang X;Lin S;Yuan L;Ouyang G
Periostin(POSTN)是一种新近鉴定的基质细胞蛋白，在多种恶性肿瘤中经常表达失调，并促进肿瘤的转移生长。POSTN在小鼠乳腺癌干细胞(CSCs)和它们的利基之间的串扰中起着关键作用，从而允许转移定植。然而，POSTN的促转移能力是否与间充质干细胞(MSCs)的多潜能相关尚未见文献报道。在这里，我们证明了POSTN促进了人乳腺上皮细胞和乳腺癌细胞的干细胞样特征和间充质表型。有趣的是，异位过表达POSTN或重组POSTN治疗可以诱导人乳腺上皮细胞和乳腺癌细胞分化为多个细胞系，从而概括了MSCs的部分多系分化潜能。此外，POSTN在体外高表达于骨髓间充质干细胞及其衍生的脂肪细胞、软骨细胞和成骨细胞。此外，POSTN还能促进体内移植瘤的生长。过表达POSTN的人乳腺上皮细胞促进乳腺肿瘤生长和转移。这些数据为POSTN在乳腺上皮性肿瘤和转移中的新作用提供了证据，提示上皮性癌细胞可能获得CSC样特性和间充质表型，以及MSCs促进肿瘤发生和转移的多潜能。因此，靶向肿瘤微环境中的POSTN和其他细胞外基质成分可能有助于开发抑制肿瘤转移的新的治疗策略。
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.