Expression of the periostin mRNA level in neuroblastoma

doi:10.1053/jpsu.2002.34985

Journal of Pediatric Surgery

Volume 37, Issue 9, September 2002, Pages 1293-1297

https://doi.org/10.1053/jpsu.2002.34985 Get rights and content

Abstract

Background: Neuroblastoma is the most common malignant solid tumor in early childhood. Whether neuroblastoma is diagnosed by mass screening or by clinical symptom, it has been reported to be correlated with prognosis of the disease. The periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Methods: Expression of periostin messenger RNAs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay in 24 tumor samples from neuroblastoma using LightCycler. The data were analyzed in reference to clinicopathologic factors. Results: There was a tendency for higher periostin transcripts levels in the tumor samples from stage IV when compared with the stage I (P =.0845). The periostin mRNA level was higher in the group with disease diagnosed by symptom than in the group with disease diagnosed by mass screening (P =.0266). The periostin mRNA level also was higher in the group with disease diagnosed after 1 year of age than in the group with disease diagnosed before 1 year of age (P =.0059). Conclusion: Because the groups with disease diagnosed by symptom or after 1 year of age were reported to be the worse prognosis, the periostin mRNA expression levels were correlated with tumor progression or prognosis of neuroblastoma. J Pediatr Surg 37:1293-1297. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patients

The study groups included 24 (14 boys, 10 girls) neuroblastoma patients who had undergone surgery at the Department of Surgery II, Nagoya City University Medical School between 1989 and 2000. The neuroblastomas were classified according to the International Neuroblastoma Staging System. Of the 24 cases, 18 were identified at less than 1 year of age, and 18 of the 24 infantile patients were identified by a mass screening system (Table 1).All tumor samples were collected at resection and

Periostin mRNA expression

Of 24 neuroblastomas studied, all of the tumor samples had periostin transcript, and the periostin/GAPDH mrRNA level was 33.231 ± 48.140 (mean ± SD). The relationship between the gene expression of periostin in neuroblastoma and the patients' clinicopathologic factors is shown in Table 1. There was no significant difference in the periostin expression between patient groups stratified according to the gender. The periostin mRNA level was significantly higher in the group diagnosed by symptom

Discussion

In the current study, periostin mRNA expression was analyzed for the first time in clinical samples of neuroblastoma. We have shown that periostin mRNA level was higher in the groups identified by symptoms or after 1 year of age in neuroblastoma. It has been shown previously that the human periostin gene is overexpressed in the lung carcinomas and correlated with worse prognosis. We showed that mRNA expression of periostin was relatively higher in the tumor with the advanced stage of

Acknowledgements

The authors thank Mrs A. Miyazaki for her excellent technical assistance.

References (23)

T Nagata et al.
The high level of human CDC10 gene expression in neuroblastoma may be associated with favorable characteristics of the tumor
J Surg Res
(2000)
S Suita et al.
Mass screening for neuroblastoma at 6 months of age: Difficult to justify
J Pediatr Surg
(1998)
H Sasaki et al.
Serum level of the periostin a homologous of a insect cell adhesion molecule, in thymoma patients
Cancer Lett
(2001)
DD Hunter et al.
Primary sequence of a motor neuron-selective adhesive site in the synaptic basal lamina protein S-laminin
Cell
(1989)
GM Brodeur et al.
Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage
Science (Washington DC)
(1984)
RC Seeger et al.
Association of multiple copies of N-myc oncogene with rapid progression of neuroblastomas
N Engl J Med
(1985)
A Yoneda et al.
Observation of untreated patients with neuroblastoma detected by mass screening: A wait and see pilot study
Med Pediatr Oncol
(2001)
A Nakagawa et al.
N-myc oncogene and stage IV-S neuroblastoma
Cancer (Phila)
(1990)
A Eggert et al.
Prognostic and biological role of neurotrophin-receptor TrkA and TrkB in neuroblastoma
Clin Pediatr
(2000)
XX Tang et al.
Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastoma
Med Pediatr Oncol
(2001)

ML Schmidt et al.

Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study

J Clin Oncol

(2000)

Cited by (47)

Targeting EP2 receptor with multifaceted mechanisms for high-risk neuroblastoma
2022, Cell Reports
Citation Excerpt :
Pearson’s correlation coefficient analyses revealed significant positive correlations of expression between EP2 and a large proportion of these cytokines, chemokines, growth factors, and receptors (40/45, ∼89%) in at least two of the four major R2 NB datasets: SEQC, Kocak, Versteeg, and NRC (Figure 1D). These potential NB facilitators include ALK (Trigg and Turner, 2018), brain-derived neurotrophic factor (BDNF) (Middlemas et al., 1999), chemokine (C-C motif) ligand 2 (CCL2) or monocyte chemoattractant protein 1 (MCP-1)/C-C chemokine receptor type 2 (CCR2) (Metelitsa et al., 2004), colony-stimulating factor 1 (CSF-1)/CSF-1 receptor (CSF1R) (Webb et al., 2018), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/CX3CR1 (Nevo et al., 2009), CXCL2/CXCR2 (Hashimoto et al., 2016), CXCL12/CXCR4/CXCR7 (Liberman et al., 2012), epidermal growth factor receptor (EGFR) (Ho et al., 2005), endoglin (ENG) or cluster of differentiation 105 (CD105) (Cavar et al., 2015; Pezzolo et al., 2007; Wu et al., 2019), glial cell line-derived neurotrophic factor (GDNF)/GDNF family receptor α1 (GFRA1) (Hansford and Marshall, 2005; Hishiki et al., 1998), insulin-like growth factor 2 (IGF2)/IGF2 receptor (IGF2R) (El-Badry et al., 1991; Mohlin et al., 2013), interleukin (IL)-1β/IL-1R (Elaraj et al., 2006), IL-6/IL-6R (Ara et al., 2013; Pistoia et al., 2011), macrophage inhibitory cytokine 1 (MIC-1) (Craig et al., 2016), matrix metallopeptidases (MMPs) (Nyalendo et al., 2009; Sugiura et al., 1998), nuclear factor κB (NF-κB) (Spel et al., 2018; Zhi et al., 2014, 2015), platelet-derived growth factor receptor β (PDGFRB) (Kock et al., 2018), platelet endothelial cell adhesion molecule 1 (PECAM-1) or CD31 (Pezzolo et al., 2007), periostin (POSTN) (Sasaki et al., 2002), retinoic acid receptor responder protein 2 (RARRES2)/chemokine-like receptor 1 (CMKLR1) (Tummler et al., 2017), signal transducer and activator of transcription 3 (STAT3) (Hadjidaniel et al., 2017), transforming growth factor β1 (TGF-β1) (Castriconi et al., 2013), vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) (Becker et al., 2010; Jakovljevic et al., 2009; Weng et al., 2017), as well as the VGF nerve growth factor inducible (Rossi et al., 1992) (Tables S1–S4). These consistent findings from analyzing the NB patient datasets reveal that the elevated EP2 expression is highly associated with the increased malignancy of NB tumors, leading us to hypothesize that PGE2 signaling via the EP2 receptor might contribute to COX activity-mediated NB growth.
Prostaglandin E₂ (PGE₂) promotes tumor cell proliferation, migration, and invasion, fostering an inflammation-enriched microenvironment that facilitates angiogenesis and immune evasion. However, the PGE₂ receptor subtype (EP1–EP4) involved in neuroblastoma (NB) growth remains elusive. Herein, we show that the EP2 receptor highly correlates with NB aggressiveness and acts as a predominant Gα_s-coupled receptor mediating PGE₂-initiated cyclic AMP (cAMP) signaling in NB cells with high-risk factors, including 11q deletion and MYCN amplification. Knockout of EP2 in NB cells blocks the development of xenografts, and its conditional knockdown prevents established tumors from progressing. Pharmacological inhibition of EP2 by our recently developed antagonist TG6-129 suppresses the growth of NB xenografts in nude mice and syngeneic allografts in immunocompetent hosts, accompanied by anti-inflammatory, antiangiogenic, and apoptotic effects. This proof-of-concept study suggests that the PGE₂/EP2 signaling pathway contributes to NB malignancy and that EP2 inhibition by our drug-like compounds provides a promising strategy to treat this deadly pediatric cancer.
Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas
2015, Oral Oncology
Citation Excerpt :
Genes associated with tumor invasion, metastasis, and recurrence were significantly differentially expressed in UK but not Sri Lankan tumors including the upregulation of MMP3, PTGS2, LAMC2, POSTN, COL11A1, and TNC along with downregulation of DUSP1 and SLPI. Likewise, significant deregulation of other genes in Sri Lankan, but not UK tumor samples have been reported to play a role in preventing tumor invasion and metastasis (elevated expression of CD80, IL1RL1, GML, CYP27B1, SCN10A, HOXC10, and SH2D2A along with reduced expression of TWIST1, RECK, PSPH, GNG11, LSM7, and ERAP2) [20–54]. Activation of ESR1, SMAD3, and SMAD4 transcription regulators in UK tumors relative to their normal comparators might also facilitate the invasive phenotypic behavior of UK tumors [55–57].
It is well recognized that oral squamous cell carcinoma (OSCC) cases from Asia that are associated with betel quid chewing are phenotypically distinct to those from Western countries that are predominantly caused by smoking/drinking, but the molecular basis of these differences are largely unknown. The aim of this study is to examine gene expression, related carcinogenic pathways and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups.
We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays. The generated data was interrogated using significance analysis of microarrays and Ingenuity Pathway Analysis (IPA).
The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other. However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka.
The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated “Cell-mediated Immune Response” in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients.
Urine periostin as a biomarker of renal injury in chronic allograft nephropathy
2014, Transplantation Proceedings
Citation Excerpt :
Currently, periostin is discussed as a major player in tissue fibrosis, but is also a critical component of mechanically challenged biological structures, including kidney tissues. Moreover, several reports describe periostin overexpression in malignant cells that had undergone EMT and metastasized [13–15]. The de novo periostin expression in the tubulointerstitium areas is most likely from myofibroblasts as described in postischemic myocardium or diseased heart valves [16].
Chronic allograft nephropathy (CAN) represents the main cause of renal allograft failure after transplantation. Noninvasive CAN testing is required. Periostin promotes the expression of a mesenchymal phenotype in renal tubules and is a promising urine biomarker for progressive renal injury. Information regarding periostin expression in the setting of CAN remains scarce.
Subjects were recruited from our outpatient transplantation clinic. Random urine samples were collected from CAN patients (n = 24) and renal transplant patients with normal renal function (transplant controls, n = 18). Control samples were collected from healthy volunteers (n = 18) who had normal renal function. Urine periostin was measured by enzyme-linked immunosorbent assay.
The median urine periostin in CAN patients was significantly higher than in transplant and healthy controls (1.74 vs 0.00 vs 0.14 ng/mg creatinine, respectively; P < .001). Urine periostin enzyme-linked immunosorbent assay at a cutoff value of 0.152 ng/mg creatinine demonstrated the sensitivity, specificity, and accuracy for distinguishing CAN patients from transplant patients with normal renal function (91.7%, 77.8%, and 85.7%, respectively). In addition, urine periostin levels correlated directly with urine protein creatinine ratio (R = 0.566, P < .001) and serum creatinine (R = 0.522; P < .001), whereas inverse significant correlations were evidenced with estimated glomerular filtration rate (R = −0.431; P < .001).
The appearance of urine periostin in CAN patients but not in healthy and transplant controls underscores its value as a potential biomarker for chronic progressive renal injury in transplant recipients.
Characterization of periostin isoform pattern in non-small cell lung cancer
2012, Lung Cancer
Citation Excerpt :
It is present in many healthy tissues such as periodontal ligament, periosteum, cardiac valves and placenta and in tissues under mechanical stress conditions [10–16]. Its up-regulation has been observed in a wide variety of cancerous tissues, such as ovarian, breast, pancreatic, head and neck carcinomas as well as in neuroblastoma [16–21]. Periostin is thought to promote EMT of carcinoma cells by targeting the crosstalk between the epidermal growth factor receptor (EGFR) and the integrins at the plasma membrane, with consecutive activation of the Akt/PKB (protein kinase B) and the FAK (focal adhesion kinase) pathway [5,17,19,22,23].
The extracellular matrix N-glycoprotein periostin (OSF-2, POSTN) is a major constituent of the desmoplastic stroma around solid tumors. It promotes tumor invasion and metastasis via epithelial-mesenchymal transition (EMT). In this study we investigated periostin expression at both RNA and protein level as well as the expression pattern of its splice isoforms in non-small cell lung cancer (NSCLC).
Thirty fresh frozen and corresponding formalin-fixed NSCLC tissues (adeno- and squamous cell carcinoma subtype, each n = 15) and their matched non-neoplastic tissues were investigated. Periostin mRNA levels were analyzed by quantitative RT-PCR. The EMT-markers periostin and vimentin were analyzed by immunohistochemistry. Laser capture microdissection allowed for analysis of periostin expression in tumor epithelia and stroma, separately. Isoform patterns were investigated by isoform-specific PCR following sequencing in NSCLC, fetal and adult normal lung tissue.
The qRT-PCR analysis showed periostin mRNA up-regulation in NSCLC tissue in relation to normal lung, with significantly higher levels in the adeno-compared to the squamous cell subtype (p < 0.05). However, protein levels in both tumor epithelia and stroma correlated with squamous cell carcinoma (p < 0.001) and larger tumor size (p < 0.05). Further, periostin tumor epithelia expression, correlated with higher tumor grade (p < 0.05). Sequence analysis detected eight periostin isoforms in fetal lung, but only five in both NSCLC and matched normal lung tissue. Among the eight isoforms, four are new and were labelled 5, 7, 8 and 9. The exclusive presence of isoforms 1 and 9 in fetal tissue suggests splice-specific regulation during lung embryogenesis. Finally, laser capture microdissection demonstrated that both tumor epithelia and stromal cells can be a source of periostin production in NSCLC.
This study represents the first analysis of periostin isoform expression patterns in NSCLC and a characterization of periostin expression in cancer versus stromal cells at both RNA and protein level.
Relevance of periostin splice variants in renal cell carcinoma
2011, American Journal of Pathology
The extracellular matrix N-glycoprotein periostin is thought to enhance tumor invasion. In this study, the expression patterns of periostin and its splice isoforms were investigated in renal cell carcinoma (RCC). Periostin mRNA expression patterns were characterized in 30 fresh-frozen RCCs in normal fetal and adult renal tissues by both isoform-specific and nonspecific RT-PCR and by gene expression array analysis. Its protein expression was analyzed by immunohistochemistry, using tissue microarrays with tissue from 1007 RCC patients. Periostin mRNA in RCC was increased, as observed in both RT-PCR and gene microarray analyses, with significantly higher expression in the clear cell than in the papillary subtype. Four of eight periostin isoforms, identified in fetal kidney by direct sequencing, have not been described to date. Three isoforms could be detected in both RCC and matched non-neoplastic tissue, and one of them was expressed more frequently in RCC. Periostin protein was detected in both mesenchymal cells of the tumor stroma and epithelial tumor cells. Greater amounts of periostin in tumor epithelia correlated with the presence of sarcomatoid differentiation, higher tumor stage, lymph node metastases, and poor overall survival in the clear cell subtype. In conclusion, periostin expression in tumor epithelia may contribute to sarcomatoid differentiation and more aggressive behavior of RCC. The presence of a tumor-associated periostin isoform suggests splice-specific regulation in RCC tissue.
Periostin promotes ovarian cancer angiogenesis and metastasis
2010, Gynecologic Oncology
Citation Excerpt :
Functionally, PN promotes the adhesion and motility of cancer cells by interacting with integrin receptors αVβ3 and αVβ5 [15]. PN overexpression also has been reported in many other human tumors including non-small cell lung cancer [16], neuroblastoma [17], breast [18], colon [19], head and neck [20], oral [21] and pancreatic cancers [22]. Upregulated PN expression or elevated PN serum levels have been reported to be correlated with tumor angiogenesis [21], metastases [19–21,23], clinical stage [24] or survival outcome [16].
Perostin (PN) has been found to be overexpressed in a variety of human malignancies including ovarian cancer. In the present study, we investigated PN expression status in a large cohort of ovarian tumors with the focus on biological influence of PN related on ovarian tumor angiogenesis and metastasis.
PN expression was determined by cDNA microarray, PN northern blot and PN IHC tissue array analyses. Exogenous PN expression in ovarian cancer cells OVCAR-3 and OV2008 were achieved through retroviral transfection and confirmed by PN western blot and ELISA. The effects of exogenous PN expression on tumor angiogenesis and metastatic growth were accessed in orthotopic mouse models. The in vitro cell adhesion, migration and invasion assays were performed to investigate the potential mechanisms involved in PN's in vivo effects.
PN was frequently overexpressed in ovarian tumors. Higher PN levels significantly correlated with clinical late stages (III/IV) and cancer recurrence. PN was produced by engineered PN-overexpressing cells at levels comparable to that of A2780 cells, an ovarian carcinoma cell line with endogenous PN expression. PN overexpression did not change cell growth rates in vitro; however it significantly promoted intraperitoneal tumor metastatic growth in immunodeficient mice, which was associated with increased tumor angiogenesis and decreased tumor cell apoptosis. In vitro purified PN promoted cell adhesion, migration, and invasion of both human umbilical endothelial cells (HUVECs) and/or ovarian cancer cells.
Our data indicate PN plays a critical role in both ovarian tumor angiogenesis and metastasis. Thus PN may represent a clinically effective new target for therapy of ovarian cancer.

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^☆: Address reprint requests to Hidefumi Sasaki, Department of Surgery II, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.

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Expression of the periostin mRNA level in neuroblastoma☆

Abstract

Section snippets

Patients

Periostin mRNA expression

Discussion

Acknowledgements

J Surg Res

J Pediatr Surg

Cancer Lett

Cell

Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage

Science (Washington DC)

Association of multiple copies of N-myc oncogene with rapid progression of neuroblastomas

N Engl J Med

Observation of untreated patients with neuroblastoma detected by mass screening: A wait and see pilot study

Med Pediatr Oncol

N-myc oncogene and stage IV-S neuroblastoma

Cancer (Phila)

Prognostic and biological role of neurotrophin-receptor TrkA and TrkB in neuroblastoma

Clin Pediatr

Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastoma

Med Pediatr Oncol

Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study

J Clin Oncol