Dataset Information

STIM1 expression is associated with osteosarcoma cell survival.

ABSTRACT: Objective:To examine the role of store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca2+ contributes to the regulation of osteosarcoma cells. Methods:First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) activity by luciferase assays. Results:STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca2+ channels involved down-regulation of NFATc1 in osteosarcoma cells. Conclusions:STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca2+ entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.

SUBMITTER: Zang J

PROVIDER: S-EPMC6433589 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

STIM1 expression is associated with osteosarcoma cell survival.

Zang Jie J Zuo Dongqing D Shogren Kristen L KL Gustafson Carl T CT Zhou Zifei Z Thompson Michael A MA Guo Ruiwei R Prakash Y S YS Lu Lichun L Guo Wei W Maran Avudaiappan A Yaszemski Michael J MJ

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20190201 1

<h4>Objective</h4>To examine the role of store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca<sup>2+</sup> contributes to the regulation of osteosarcoma cells.<h4>Methods</h4>First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 o ...[more]

PMID: 30996578

Similar Datasets

Project description:BackgroundGene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS.ResultsThe 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans.ConclusionA molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression.

Project description:Objectives:Previous genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression. Methods:A total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from 72 patients during surgery. The gene expression level of IL33 and GLDC was evaluated by qPCR. Patients were classified into two groups according to the 5-year overall survival (death/survival). The chi-square test was used to analyze difference of genotype frequency. The Student t-test was used to compare the gene expression level between different genotypes. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Results:Genotype TT of rs55933544 was significantly associated with the event of death (0.176 vs. 0.061, p < 0.001). Patients with no risk allele T of rs55933544 showed a 5-year overall survival of 81.4% (110/141), which was significantly higher than an overall survival of 55.0% (29/54) for patients with one risk allele and 44.8% (12/21) for patients with two risk alleles (p < 0.01). Genotype TT of rs55933544 were indicative of remarkably lower expression of IL33 than genotype CC (0.00041 ± 0.00025 vs. 0.00065 ± 0.00031, p = 0.04). Patients with low IL33 expression presented remarkably worse survival as compared with the patients with high IL33 expression (p < .01). Conclusions:Variant rs55933544 was associated with the survival time of OS patients. IL33 may contribute to a poor prognosis of OS. Further investigation into the biological mechanisms by which IL33 influences the overall survival can shed light on the improvement of clinical outcome for OS patients.

Dataset Information

STIM1 expression is associated with osteosarcoma cell survival.

Publications

STIM1 expression is associated with osteosarcoma cell survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets