βIG-H3, a Novel Secretory Protein Inducible by Transforming Growth Factor-β, Is Present in Normal Skin and Promotes the Adhesion and Spreading of Dermal Fibroblasts In Vitro

LeBaron, Richard G.; Bezverkov, Kelly; Zimber, Michael; Pavelec, Rebecca; Skonier, John E.; Purchio, Anthony F.

doi:10.1111/1523-1747.ep12607024

Cited by 205 publications

(163 citation statements)

References 35 publications

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“…Periostin has a typical signal sequence, followed by a cysteine-rich domain, four repeated and conserved domains and a C-terminal hydrophilic domain (Takeshita et al, 1993;Horiuchi et al, 1999). A similar structure was reported for fasciclin I, a cell adhesion molecule involved in the development of the central nervous system of insects (Zinn et al, 1988), and for the big-h3 molecule, a secreted protein induced by TGF-b1 which promotes the attachment and spreading of fibroblasts (Skonier et al, 1992;LeBaron et al, 1995). Periostin was found to be overexpressed in various types of human cancer such as lung (Sasaki et al, 2001a), brain (Sasaki et al, 2002), ovary (Gillan et al, 2002), breast (Shao et al, 2004) and colon cancers Tai et al, 2005) and elevated levels have been detected in sera of patients with thymoma (Sasaki et al, 2001b), non-small lung carcinoma (Sasaki et al, 2001c) and breast cancer (Sasaki et al, 2003).…”

Section: Introductionmentioning

confidence: 68%

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

Baril¹,

Gangeswaran²,

Mahon³

et al. 2006

Oncogene

257

244

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Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a rapid progression and poor treatment response. Using gene expression profiling of pancreatic cancer tissues, we previously identified periostin as a potential diagnostic and therapeutic target. In this study, we report the overexpression of periostin in a larger set of pancreatic cancer tissues and show that although the periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells. Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly increased levels of periostin in the sera of pancreatic cancer patients compared to non-cancer controls. We demonstrate that periostin promotes the invasiveness of tumour cells by increasing the motility of cells without inducing expression of proteases, and enhances the survival of tumour cells exposed to hypoxic conditions. At the molecular level, we provide evidence that the a 6 b 4 integrin complex acts as the cell receptor of periostin in pancreatic cancer cells and that interaction promotes phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but not the RAS/MEK/ERK pathway. These findings suggest an important role of periostin in pancreatic cancer and provide a rationale to study periostin for diagnostic and therapeutic applications.

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Section: Introductionmentioning

confidence: 68%

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

Baril¹,

Gangeswaran²,

Mahon³

et al. 2006

Oncogene

257

244

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“…Periostin from osteoblasts was originally identified to function as a cell adhesion molecule for preosteoblasts and precipitate in osteoblast recruitment, attachment and spreading. 16,17 Recently, proteomic and microarray profiling studies showed that periostin is up-regulated in pancreatic cancer tissues. [18][19][20] However, it has been demonstrated that periostin protein was mainly detected in the juxtatumoral stroma components, while the tumor cells themselves showed no immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Kanno

Satoh

Masamune

et al. 2008

Intl Journal of Cancer

123

103

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Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 lg/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer. ' 2008 Wiley-Liss, Inc.Key words: pancreatic cancer; periostin; EMT; pancreatic stellate cell Pancreatic adenocarcinoma is one of the most malignant gastrointestinal tumors. Once pancreatic cancer is clinically evident, it progresses rapidly to develop metastatic lesions, frequently by the time of diagnosis. The pathogenic mechanisms that regulate the aggressive behavior of this cancer still remain to be clarified.Tumor metastasis is a multistep pathological process involved in the final phase of tumor development. During this process, epithelium-derived tumor cells undergo fibroblast-like transformation, referred to as epithelial-mesenchymal transition (EMT). 1,2 EMT is the process by which an epithelial cell shows transitory changes in cell structure and becomes a more motile mesenchymal cell with migratory properties during embryogenesis. This transition is considered to be an important event during malignant tumor progression and metastasis. [3][4][5] Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule for preosteoblasts and to participate in osteoblast recruitment, attachment and spreading. 6,7 Recently, the expression of periostin has been implicated in the development of variety of carcinomas such as neuroblastoma, 8 epithelial ovarian cancer 9 and non-small cell lung carcinoma. 10 P...

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“…This is the first evidence that Betaig-h3 gene has tumour suppressor function in a human epithelium-derived tumour model. Betaig-h3 is a secreted protein that promotes the adhesion of dermal fibroblasts and corneal epithelial cells (LeBaron et al, 1995;Billings et al, 2000a,b;). These findings imply that Betaigh3 gene affects cell -ECM interaction by regulating integrin receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that Betaig-h3 protein affect cell -ECM interaction through regulation of integrin receptor (LeBaron et al, 1995;Billings et al, 2000a,b). Using cDNA array, it was found The blots were hybridised to 32 P-labelled Betaig-h3 cDNA probes.…”

Section: Betaig-h3 Gene Is Related To the Expression Level Of Integrimentioning

confidence: 98%

“…There is evidence that mutations or altered expression of this gene are involved in corneal dystrophy and osteogenesis in human (Bron, 2000;Kim et al, 2000a). In addition, Betaig-h3 protein is a component of ECM in lung, bladder and skin (LeBaron et al, 1995;Billings et al, 2000a,b), which promotes adhesion and the spreading of dermal fibroblasts in vitro and mediates cell adhesion by interacting with a3b1 integrin in human corneal epithelial cells (Billings et al, 2000b;Kim et al, 2000b). These data suggest that Betaig-h3 protein is involved in cellular adhesion and imply an important role of this gene in the process of human tumour progression.…”

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confidence: 99%

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Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

2002

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{Interaction between cell and extracellular matrix plays a crucial role in tumour invasion and metastasis. Using an immortalised human bronchial epithelial (BEP2D) cell model, the study here shows that expression of Betaig-h3 gene, which encodes a secreted adhesion molecule induced by transforming growth factor-b, is markedly decreased in several independently generated, radiation-induced tumour cell lines (TL1 -TL5) relative to parental BEP2D cells. Transfection of Betaig-h3 gene into tumour cells resulted in a significant reduction in tumour growth. While integrin receptor a5b1 was overexpressed in tumour cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumour progression by regulating integrin receptor a5b1. The findings provide strong evidence that the Betaig-h3 gene has tumour suppressor function in human BEP2D cell model and suggest a potential target for interventional therapy.

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βIG-H3, a Novel Secretory Protein Inducible by Transforming Growth Factor-β, Is Present in Normal Skin and Promotes the Adhesion and Spreading of Dermal Fibroblasts In Vitro

Cited by 205 publications

References 35 publications

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

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