High periostin expression correlates with aggressiveness in papillary thyroid carcinomas

Periostin is a mesenchyme-specific gene product, which acts as an adhesion molecule during bone formation and supports osteoblastic cell line attachment and spreading. However, periostin expression is activated in a large variety of epithelial human tumors and correlates with their aggressiveness. Knowledge of expression of periostin in thyroid tumors is still scanty. The aim of the present work was to investigate periostin expression in differentiated neoplasms of the thyroid and to correlate it with several clinical and molecular features of these tumors. Periostin expression was evaluated by quantitative PCR and immunohistochemistry in normal thyroid tissues, papillary thyroid carcinomas (PTCs), follicular thyroid carcinomas (FTCs), and follicular adenomas (FAs). Periostin mRNA levels were also evaluated in several thyroid tumor cell lines. PTCs show mean periostin mRNA levels significantly higher than corresponding normal tissues. In five PTCs, periostin mRNA values were at least 30-fold higher than corresponding normal tissues. Conversely, mean periostin mRNA levels of FTCs and FAs were similar to those of normal tissues. Consistent with mRNA studies, periostin was detectable by immunohistochemistry in cancerous epithelial cells only in several cases of PTCs but not in normal tissue, FTCs, and FAs. In PTCs, periostin mRNA levels positively correlate with extrathyroidal invasion, distant metastasis, and higher grade staging. A negative correlation between periostin and expression of some markers of the thyroid-differentiated phenotype (thyroglobulin, thyrotropin receptor) was also present in the PTCs. These results indicate that an increase in periostin gene expression is present in several PTCs, in which it appears as a marker of aggressiveness. Experiments in thyroid tumor cell lines indicate that high levels of periostin mRNA are due, at least in part, to the increase in periostin promoter activity.

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Status and expression of thep16INK4 gene in human thyroid tumors and thyroid-tumor cell lines

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19960703)67:1<29::aid-ijc7>3.0.co;2-1 ◽

1996 ◽

Vol 67 (1) ◽

pp. 29-34 ◽

Cited By ~ 18

Author(s):

Viola Calabr� ◽

Maria Strazzullo ◽

Girolama La Mantia ◽

Monica Fedele ◽

Christian Paulin ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Thyroid Tumor ◽

Human Thyroid ◽

Thyroid Tumors ◽

Tumor Cell Lines

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Thrombopoietin Receptor Levels in Tumor Cell Lines and Primary Tumors

Journal of Oncology ◽

10.1155/2010/135354 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Connie L. Erickson-Miller ◽

Antony Chadderton ◽

Anna Gibbard ◽

Jennifer Kirchner ◽

Kodandaram Pillarisetti ◽

...

Keyword(s):

Growth Factor ◽

Tumor Cell ◽

Cell Lines ◽

Hematologic Malignancies ◽

Erythropoietin Receptor ◽

Tumor Cell Lines ◽

Hepatitis C Infection ◽

Primary Tumors ◽

Normal Tissues ◽

Proliferation And Differentiation

Thrombopoietin (TPO) receptor agonists represent a new approach for the treatment of thrombocytopenia, which may develop as a consequence of immune thrombocytopenia, chemotherapy treatment, chronic hepatitis C infection, or myelodysplastic syndromes. There are concerns that use of certain growth factors can hasten disease progression in some types of hematologic malignancies and solid tumors. In this study, expression ofMPL(TPO-R) mRNA was examined in tumor cell lines, patient tumor samples (renal cell carcinoma, prostatic carcinoma, soft tissue and bony/cartilage sarcoma, colon cancer, and lymphoma), and normal tissues using microarray analysis and qRT-PCR.MPLmRNA is expressed at very low or undetectable levels compared with erythropoietin receptor (EPOR), human epidermal growth factor (ERBB2; HER2), and insulin-like growth factor-1 receptor (IGF1R) in these patient samples. These data suggest TPO-R agonists will likely preferentially stimulate proliferation and differentiation of cells of megakaryocytic lineage, potentially demonstrating their utility for correcting thrombocytopenia in clinical settings.

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Expression of Matrix Metalloproteinases and Their Specific Inhibitors in Normal and Different Human Thyroid Tumor Cell Lines

Thyroid ◽

10.1089/thy.2004.14.881 ◽

2004 ◽

Vol 14 (11) ◽

pp. 881-888 ◽

Cited By ~ 31

Author(s):

E. Baldini ◽

M. Toller ◽

F.M. Graziano ◽

F.P. Russo ◽

M. Pepe ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Tumor Cell ◽

Cell Lines ◽

Thyroid Tumor ◽

Human Thyroid ◽

Tumor Cell Lines ◽

Specific Inhibitors

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Eltrombopag Decreases Proliferation of Ovarian, Lung and Breast Tumor Cell Lines.

Blood ◽

10.1182/blood.v114.22.2409.2409 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2409-2409

Author(s):

Connie L. Erickson-Miller ◽

Jennifer Kirchner ◽

Kodandaram Pillarisetti ◽

Lone Ottesen ◽

Yasser Mostafa Kamel ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cell ◽

Cell Lines ◽

Mrna Levels ◽

Tumor Cell Lines ◽

Employment Equity ◽

Qrt Pcr ◽

Thrombopoietin Receptor ◽

Equity Ownership ◽

Low Levels

Abstract Abstract 2409 Poster Board II-386 Background: Eltrombopag (Promacta®) is a novel, oral thrombopoietin receptor (TpoR) agonist that interacts with the TpoR on bone marrow progenitors to stimulate megakaryocyte production, thus increasing platelet counts in thrombocytopenic patients. The effects of eltrombopag on the proliferation of solid tumor cell lines and the expression of thrombopoietin receptor (MPL, TpoR) on patient tumors is of interest given that chemotherapy can cause thrombocytopenia. Materials and methods: Proliferation was measured by Cell Titer Glo assay on 3 ovarian (OVCAR3, OVCAR4, SKOV3), 4 lung (A549, NCI-H226, NCI-H510, NCI-H460) and 3 breast (BT-474, MCF7, HCC1937) cancer cell lines from the ATCC treated with 0.01 – 100 ug/mL eltrombopag. Quantitative RT-PCR (qRT-PCR) for MPL expression was performed on the tumor cell lines and on 40 tumor samples, each from subjects with ovarian, lung or breast cancer. Microarray analysis for MPL mRNA expression was examined from 118 subjects with breast cancer and 29 with non-small cell lung cancer (NSCLC). Microarray data was normalized using robust multiarray average (RMA) and relative mRNA expression was determined. To determine expression of TpoR protein, western blot analyses was performed on some of the tumor cell lines. Results: Eltrombopag induced an inhibition of proliferation on all of the ovarian, lung and breast solid tumor cell lines tested. The IC50 ranged from 3.7 to 49.7 ug/mL (see table below). The Cmax of ITP patients treated with 75 mg eltrombopag is 11.4 ug/mL, demonstrating that these concentrations are clinically achievable. There was no enhancement of proliferation at any concentration of eltrombopag, consistent with the very low or undetectable level of MPL expression on samples of tumors from patients with these diseases. MPL was expressed at very low or undetectable levels in these tumor cell lines with the exception of the lung cancer line, NCI-H510. However, western blot analyses showed no detectable TpoR protein expression regardless of the higher levels of MPL mRNA in NCI-H510 cells. Erythropoietin receptor (EPOR) mRNA was expressed at low-to-moderate levels, while ERBB2 and IGF1R were expressed at higher levels in these cell lines. Microarray analysis showed undetectable MPL mRNA levels in all 118 samples from patients with breast cancer and 52% of the NSCLC samples, the remaining NSCLC samples expressed low levels of MPL. In contrast, EPOR was expressed in 75–100% of the breast cancer, and NSCLC samples. ERBB2 was expressed in 97–100% of the samples and IGF1R was expressed in 54–100% of the samples. When 40 other tumor samples each from subjects with ovarian, lung and breast cancer were examined by qRT-PCR, MPL mRNA levels were also very low or undetectable. EPOR, ERBB2, and IGF1R expression levels varied according to tumor type, but were greater than MPL levels. Conclusions: In summary, similar to its effects on leukemia and lymphoma cell lines, all of the nine lung, ovarian, breast or prostate tumor cell lines demonstrated decreased proliferation in response to eltrombopag. The undetectable or very low levels of expression of MPL mRNA in tumors of patients with lung, ovarian, breast or prostate cancer supports the proliferation results. Disclosures: Erickson-Miller: GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties, Research Funding. Kirchner:GlaxoSmithKline: Employment. Pillarisetti:GSK: Employment, Equity Ownership, Patents & Royalties. Ottesen:GSK: Employment, Equity Ownership. Mostafa Kamel:GSK: Employment, Equity Ownership. Liu:GSK: Employment, Equity Ownership. Martin:GSK: Employment, Equity Ownership. Messam:GSK: Employment, Equity Ownership.

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Tumor-suppressive activity of the growth arrest-specific gene GAS1 in human tumor cell lines

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19980209)75:4<568::aid-ijc13>3.0.co;2-5 ◽

1998 ◽

Vol 75 (4) ◽

pp. 568-577 ◽

Cited By ~ 32

Author(s):

Andreas Evdokiou ◽

Prudence A. Cowled

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Growth Arrest ◽

Human Tumor ◽

Specific Gene ◽

Tumor Cell Lines ◽

Suppressive Activity ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

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RNA interference against Biot2, a novel mouse testis — specific gene, inhibits the growth of tumor cells

Cellular & Molecular Biology Letters ◽

10.2478/s11658-009-0004-6 ◽

2009 ◽

Vol 14 (3) ◽

Cited By ~ 2

Author(s):

Chun-Ting Wang ◽

Peng Zhang ◽

Yong-Sheng Wang ◽

Xu-Zhi Ruan ◽

Zhi-Yong Li ◽

...

Keyword(s):

Rna Interference ◽

Tumor Cell ◽

Cell Lines ◽

Cancer Cell Line ◽

Brdu Incorporation ◽

Specific Gene ◽

Tumor Cell Lines ◽

Rt Pcr

AbstractBiot2 is a novel murine testis-specific gene that was first identified using the SEREX technique, and named by our laboratory. Using conventional RT-PCR and real time RT-PCR, we tested the expression profile of Biot2 in normal tissues and various murine tumor cell lines. Using RNA interference, we studied the biological function of Biot2 in tumorigenesis. We applied various types of growth assay, such as the in vitro MTT, colony-forming and BrdU incorporation assays, along with in vivo tumorigenicity assays, to reveal its inhibition of tumor cell proliferation. The results revealed that the Biot2 transcript was detected only and strongly in the testis tissues and abundantly in five types of murine cancer cell line. Treating B16 murine melanoma, LL/2 murine Lewis lung carcinoma and CT26 murine colorectal adenocarcinoma with special shRNA targeting Biot2 can significantly reduce the proliferation rate of these three tumor cell lines in vitro, as measured by the MTT, colony-forming and BrdU incorporation assays. The tumorigenicity of the CT26 cells transfected with special shRNA targeting Biot2 was also decreased distinctly in vivo compared with the control. It was therefore concluded that Biot2 plays a key role in tumorigenesis and could be a potential target for biotherapy.

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A CD8+ T-Cell Clone Directed Against AML Blasts that Recognizes a Tumor Specific Antigen Expressed Also by Solid Tumors

Blood ◽

10.1182/blood.v116.21.4289.4289 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4289-4289

Author(s):

Angela Rita Elia ◽

Paola Circosta ◽

Russo Vincenzo ◽

Lia Mele ◽

Bernardino Allione ◽

...

Keyword(s):

Tumor Cell ◽

Cell Line ◽

Mhc Class I ◽

Cell Lines ◽

Negative Control ◽

Leukemic Cells ◽

Tumor Cell Lines ◽

Leukemic Stem Cells ◽

Normal Tissues ◽

Restriction Element

Abstract Abstract 4289 The aim of this study was to generate cytotoxic T-lymphocytes (CTL) clones directed against AML cells and to identify new immunogenic antigens with the following properties: i) to be overexpressed by leukemic cells and not by normal tissues; ii) to be shared among different AML subtypes; iii) to play a role in leukemic growth/survival; iv) to be expressed by leukemic stem cells. To this end, we loaded normal dendritic cells (DC) from a healthy donor with apoptotic bodies from primary AML cells and used loaded DC to stimulate autologous lymphocytes (i.e. lymphocytes from the donor). Donor was selected to be partially matched with the leukemic patient for MHC-class I, in that he shared two MHC-class I alleles at the HLA-supertype level (HLA-B7 and HLA-B44). With this strategy, a CD8+ T-cell line was generated that recognized both loaded DC and AML cells used for loading, but not DC loaded with normal cells derived from the patient (PHA-blasts). This CTL line was cloned by limiting dilutions and 180 clones were screened by IFN-g elispot against 2 different AML samples that were expressing both HLA-B7 and HLA-B44; one additional mismatched AML sample was used as negative control. Two clones were selected that recognized HLA-B7+/HLA-B44+ AML cells but not the negative control (namely, clone 31D3 and 8E12). To determine the HLA-restriction element and to verify shared antigen expression among AML subtypes, we tested both clones against a panel of 18 HLA-typed primary AML samples. We found that clone 31D3 was restricted by HLA-B7 and clone 8E12 by HLA-B44. Each clone recognized 5/5 HLA-matched AML samples of different subtype. In addition, the clones did not recognize both resting and activated normal myeloid, nor lymphoid and CD34+ cells expressing the proper HLA-restriction allele. In addition to elispot activity, both clones showed killing of AML cells in a CFSE-based cytotoxic assay. To confirm the lack of reactivity against normal tissues, we analyzed the activity of both clones against HLA matched or mismatched fibroblasts and we found that clone 8E12 displayed a low reactivity activity against normal matched fibroblasts, while clone 31D3 was not reactive. We then focused the analysis on clone 31D3 and tested whether its activity was restricted to leukemia or also directed against a panel of HLA-B7 positive (N=3) or negative (N=5) solid tumors. Interestingly, we found that the clone 31D3 could recognize one colon carcinoma and one melanoma cell line expressing the HLA-B7 supertype. In particular, the melanoma cell line (G4-mel) was HLA-B35+ (HLA-B35 belongs to the HLA-B7 supertype) and was recognized at very high levels. The availability of a tumor cell line expressing adequate amounts of antigen will make the generation of a cDNA library for antigen identification more feasible than with primary leukemic cells. Finally, to further confirm that HLA-B35 is the proper MHC restriction element and to determine to what extent the antigen is shared among different tumors, we transduced 8 tumor cell lines, 3 normal B-lymphoblastoid and 1 fibroblast cell line with the HLA-B35 allele. Clone 31D3 efficiently recognized 6/8 HLA-B35 transduced tumor cell lines (1 AML, 2 melanomas, 2 colon and 1 breast carcinoma) but none of the control cell lines. In conclusion, clone 31D3 is restricted by the HLA-B7 supertype, it recognizes an antigen that is expressed by leukemic cells and not by normal tissues and, most importantly, is shared among tumors of different histology. Since the vast majority of malignant cells tested (both primary cells and in vitro established cell lines) were targeted by this clone, the putative antigen might be a protein playing an important role in tumor growth or survival. We are now testing the activity of the clone against purified leukemic stem cells and attempting to identify this shared tumor antigen. Disclosures: No relevant conflicts of interest to declare.

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