Periostin Creates a Tumor-Supportive Microenvironment in the Pancreas by Sustaining Fibrogenic Stellate Cell Activity

Erkan, Mert; Kleeff, Jörg; Gorbachevski, Andre; Reiser, Carolin; Mitkus, Tomas; Espósito, Irene; Giese, Thomas; Büchler, Markus W.; Giese, Nathalia A.; Frieß, Helmut

doi:10.1053/j.gastro.2007.01.031

Cited by 278 publications

(331 citation statements)

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“…Consistently, quantitative real-time RT-PCR revealed that periostin was not or very faintly expressed in pancreatic cancer cell lines, but it was strongly expressed in PSC. 12,13 In agreement with these findings, we also showed much higher levels of both periostin mRNA and protein in stromal lesions compared with those in cancer cells. In addition, PSC expressed larger amounts of periostin than cancer cells did.…”

Section: Discussionsupporting

confidence: 89%

“…12 It has been suggested that an interaction between cancer cells and stromal cells plays a pivotal role in cancer development since a pancreatic cancer cell supernatant stimulated the secretion of periostin from pancreatic satellite cells (PSC). 13 These findings raise the question of whether or not periostin can lead pancreatic cancer cells to the state of EMT through epithelial-mesenchymal interaction.Here, we investigated the functional role of periostin during tumor progression in vitro and in vivo. We demonstrated that stromal cells were important sources of periostin and that pancreatic cancer cells increased the expression of periostin in PSC, which suppressed tumor metastasis through the blockade of EMT.…”

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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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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

mentioning

confidence: 99%

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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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“…Also, PN is reported to be up-regulated in the metastases of colorectal and liver cancers, suggesting its role in promoting tumor growth. Increased expression of PN has been associated with advanced carcinogenesis and cell proliferation, adhesion and migration (6)(7)(8). PN expression was readily detectable in breast tumor samples, while it was undetectable in normal breast tissue (9).…”

Section: Introductionmentioning

confidence: 99%

Role of periostin in cancer progression and metastasis: Inhibition of breast cancer progression and metastasis by anti-periostin antibody in a murine model

Kyutoku

Taniyama

Katsuragi³

et al. 2011

Int J Mol Med

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Abstract. Periostin (PN), a secreted adhesion-related protein expressed in the periosteum and periodontal ligaments, acts as a critical regulator of the formation and maintenance of bone and teeth, and also plays an important role in tumorigenesis. Although PN is highly expressed in various types of human cancers, its function is still unclear. In this study, we focused on the exon 17 region of PN, which is alternatively spliced out. To investigate the function of full-length PN with exon 17, we produced a neutralizing antibody (PN1-Ab) against the peptide encoded by exon 17. In vivo, administration of PN1-Ab significantly inhibited the growth of primary tumors as well as metastatic tumors, associated with prevention of bone destruction, resulting in increased survival of mice. consistent with in vivo data, the present in vitro study demonstrated that addition of full-length PN significantly inhibited cell adhesion and detached adherent cells, while PN1-Ab inhibited the action of PN in a dose-dependent manner. In addition, PN1-Ab significantly inhibited the proliferation, migration and invasion of 4T1 mouse breast cancer cells, which produced PN. Interestingly, PN1-Ab also inhibited the differentiation of osteoclasts. Overall, the present study demonstrated that PN plays a pivotal role in the progression and metastasis of breast cancer. Since administration of PN1-Ab prolonged cell survival through inhibition of the progression and metastasis of 4T1 cells, further development of the PN1-Ab such as generation of a humanized antibody may provide a new therapeutic agent against breast cancer.

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“…POSTN encodes the extra-cellular matrix protein periostin, originally identified as a TGFβ-1-inducible protein in osteoblasts (osteoblast-specific factor 2 [14]). Periostin is highly expressed during the earliest stages of bone fracture repair [15] and vascular injury [16] and periostin signaling induces the expression of molecules associated with cutaneous wound repair such as collagen and fibronectin [17,18]. A role in cancer cell metastasis has also been suggested, as periostin is a recognize component of stromal reactions in a variety of tumor types [19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

Vi¹,

Feng²,

Zhu³

et al. 2009

Experimental Cell Research

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Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostinwas found to differentially regulate the apoptosis, proliferation, α smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

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Periostin Creates a Tumor-Supportive Microenvironment in the Pancreas by Sustaining Fibrogenic Stellate Cell Activity

Cited by 278 publications

References 50 publications

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

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

Role of periostin in cancer progression and metastasis: Inhibition of breast cancer progression and metastasis by anti-periostin antibody in a murine model

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

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