Periostin Contributes to the Acquisition of Multipotent Stem Cell-Like Properties in Human Mammary Epithelial Cells and Breast Cancer Cells

Wang, Xiaowei; Liu, Jia; Wang, Zhe; Huang, Yangmei; Liu, Weiping; Zhu, Xiao; Cai, Yao; Fang, Xiaoguang; Lin, Shu-Yong; Li, Yuan; Ouyang, Gaoliang

doi:10.1371/journal.pone.0072962

Cited by 62 publications

(58 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings complement work from others, which showed that ectopic expression of POSTN promotes stem-like properties in human mammary epithelial cells (46). Our data also support a major role for the integrin α v β 3 receptor in sustaining mammosphere growth and an ALDH-positive subpopulation.…”

Section: Discussionsupporting

confidence: 89%

Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Lambert

Wong

Öztürk

et al. 2016

Molecular Cancer Research

View full text Add to dashboard Cite

Basal-like breast cancer (BLBC) is an aggressive subtype of breast cancer which is often enriched with cancer stem cells (CSCs), but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin αvβ3, are highly expressed in a subset of BLBC cell lines as well as in cancer stem cell-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin β3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-κB-mediated transcription of key cytokines, namely IL6 and IL8, which in turn control downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.

show abstract

Section: Discussionsupporting

confidence: 89%

Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Lambert

Wong

Öztürk

et al. 2016

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Proliferative index Ki67 was reduced in metastatic deposits of 2H6-treated mice only (Fig. 4f), and we noted concomitant attenuation of Notch target genes ( Hes1 , Hey1 , Hey2 , HeyL ), as well as key mediators of metastasis, such as periostin , MMP7 , MMP9 [14, 15] (Fig. 4g, h).…”

Section: Resultsmentioning

confidence: 78%

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells

Filipović

Lombardo

Fronato

et al. 2014

Breast Cancer Res Treat

View full text Add to dashboard Cite

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancies and solid tumours with major pharmaceutical activity to identify optimal inhibitors. Within GS, nicastrin (NCSTN) offers an opportunity for therapeutic intervention using blocking monoclonal antibodies (mAbs). Here we explore the role of anti-nicastrin monoclonal antibodies, which we have developed as specific, multi-faceted inhibitors of proliferation and invasive traits of triple-negative breast cancer cells. We use 3D in vitro proliferation and invasion assays as well as an orthotopic and tail vail injection triple-negative breast cancer in vivo xenograft model systems. RNAScope assessed nicastrin in patient samples. Anti-NCSTN mAb clone-2H6 demonstrated a superior anti-tumour efficacy than clone-10C11 and the RO4929097 small molecule GS inhibitor, acting by inhibiting GS enzymatic activity and Notch signalling in vitro and in vivo. Confirming clinical relevance of nicastrin as a target, we report evidence of increased NCSTN mRNA levels by RNA in situ hybridization (RNAScope) in a large cohort of oestrogen receptor negative breast cancers, conferring independent prognostic significance for disease-free survival, in multivariate analysis. We demonstrate here that targeting NCSTN using specific mAbs may represent a novel mode of treatment for invasive triple-negative breast cancer, for which there are few targeted therapeutic options. Furthermore, we propose that measuring NCSTN in patient samples using RNAScope technology may serve as companion diagnostic for anti-NCSTN therapy in the clinic.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-3119-z) contains supplementary material, which is available to authorized users.

show abstract

“…It is frequently dysregulated in various malignant cancers and promotes tumor metastatic growth [25] since it is produced by cancerassociated fibroblasts thereby supporting, for example, growth of gastric cancer [26] or breast-cancer-derived metastases [27]. Therefore, in tumor biology, periostin presents as a possible target within the tumor microenvironment to be eliminated in order to inhibit metastasis.…”

Section: Periostin and Tumorigenesismentioning

confidence: 99%

Periostin Secreted by Mesenchymal Stem Cells Supports Tendon Formation in an Ectopic Mouse Model

Noack

Seiffart

Willbold

et al. 2014

Stem Cells and Development

View full text Add to dashboard Cite

True tendon regeneration in human patients remains a vision of musculoskeletal therapies. In comparison to other mesenchymal lineages the biology of tenogenic differentiation is barely understood. Specifically, easy and efficient protocols are lacking that might enable tendon cell and tissue differentiation based on adult (stem) cell sources. In the murine mesenchymal progenitor cell line C3H10T½, overexpression of the growth factor bone morphogenetic protein 2 (BMP2) and a constitutively active transcription factor, Smad8 L + MH2, mediates tendon cell differentiation in vitro and the formation of tendon-like tissue in vivo. We hypothesized that during this differentiation secreted factors involved in extracellular matrix formation exert a major impact on tendon development. Gene expression analyses revealed four genes encoding secreted factors that are notably upregulated: periostin, C-type lectin domain family 3 (member b), RNase A4, and follistatin-like 1. These factors have not previously been implicated in tendon biology. Among these, periostin showed a specific expression in tenocytes of adult mouse Achilles tendon and in chondrocytes within the nonmineralized fibrocartilage zone of the enthesis with the calcaneus. Overexpression of periostin alone or in combination with constitutively active BMP receptor type in human mesenchymal stem cells and subsequent implantation into ectopic sites in mice demonstrated a reproducible moderate tenogenic capacity that has not been described before. Therefore, periostin may belong to the factors contributing to the development of tenogenic tissue.

show abstract

Periostin Contributes to the Acquisition of Multipotent Stem Cell-Like Properties in Human Mammary Epithelial Cells and Breast Cancer Cells

Cited by 62 publications

References 47 publications

Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells

Periostin Secreted by Mesenchymal Stem Cells Supports Tendon Formation in an Ectopic Mouse Model

Contact Info

Product

Resources

About