scholarly journals Murine malignant cells synthesize a 19,000-dalton protein that is physicochemically and antigenically related to the immunosuppressive retroviral protein, P15E.

1983 ◽  
Vol 158 (3) ◽  
pp. 885-900 ◽  
Author(s):  
G J Cianciolo ◽  
M E Lostrom ◽  
M Tam ◽  
R Snyderman

Murine tumors contain low molecular weight factors that inhibit macrophage accumulation at inflammatory foci. Certain oncogenic murine leukemia viruses contain similar inhibitory activity and the active component of the retroviruses was shown to be the envelope protein P15E. A number of murine malignant and nonmalignant cell lines, as well as primary tumors, have now been examined to determine whether production of retroviral P15E or a related protein is characteristic of neoplastic cells. Tumor lines examined included the Hep 129 hepatocarcinoma, BP8 fibrosarcoma, RL1 lymphoma, and three variants of the B16 melanoma. Tumor lines were virus negative by electron microscopy. Nonmalignant cells examined included ST0, 3T3/BALB, and 3T3/L1 fibroblasts and unstimulated, as well as mitogen-stimulated murine splenocytes. Cells were pulse-labeled with [35S]methionine, proteins immunoprecipitated with two monoclonal antibodies to P15E and analyzed by SDS-PAGE and gel fluorography. All tumor lines synthesized a approximately 19,000-dalton protein that co-migrated with retroviral P15E on SDS-PAGE. None of the nonmalignant cells synthesized this protein. Two-dimensional gel electrophoresis of the proteins precipitated from two B16 melanoma lines by monoclonal anti-P15E showed them to be physicochemically similar to P15E from Rauscher leukemia virus. A competition ELISA assay for P15E was developed and confirmed the results obtained by metabolic labeling and demonstrated P15E-related antigens in the tumor cell lines and also in the ascites fluid of mice injected with Hep 129 cells. More importantly, P15E antigens were expressed in both a spontaneous mammary adenocarcinoma and in a primary methylcholanthrene-induced fibrosarcoma. Nonmalignant tissues from animals bearing these tumors contained no detectable P15E antigen. Extracts from the primary fibrosarcomas, when injected into the thighs of mice, inhibited the intraperitoneal accumulation of inflammatory macrophages. The inhibitory activity was specifically removed by absorption with monoclonal antibody to P15E. These results suggest that synthesis of the immunosuppressive retroviral protein P15E, or a very similar protein, routinely occurs during the growth of murine neoplastic cells. This P15E-related protein is present in spontaneous murine primary tumors as well as in all murine tumor cell lines tested. The expression of such proteins by transformed cells in vivo could confer a selective advantage for their sustained growth since they would be more likely to escape immune surveillance.

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Connie L. Erickson-Miller ◽  
Antony Chadderton ◽  
Anna Gibbard ◽  
Jennifer Kirchner ◽  
Kodandaram Pillarisetti ◽  
...  

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.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14123-14123
Author(s):  
E. M. Lackner ◽  
M. T. Krauth ◽  
R. Kondo ◽  
L. Rebuzzi ◽  
K. Eigenberger ◽  
...  

14123 Background: Tumor progression and metastasis formation are often associated with enhanced angiogenesis and with the formation of malignant effusions. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and a mediator of vascular permeability. We here describe that VEGF is produced and secreted by neoplastic cells in various solid tumors and its production mediated through mTOR. Methods and Results: As assessed by ELISA, the VEGF protein was detected in supernatants of cell lines derived from breast cancer (MDA-MB231), pancreatic carcinoma (BxPC-3), lung cancer (A-427), colon carcinoma (HCT8), and cholangiocellular carcinoma (EGI-1). In addition, VEGF was detected in supernatants of primary tumor cells obtained from malignant effusions in various malignancies (breast cancer, n=4; pancreatic cancer, n=1; ovarial cancer, n=1; parotic carcinoma, n=1; oesophageal carcinoma, n=1). In each case, VEGF protein was detectable in neoplastic cells by immunocytochemistry, and was found to accumulate in supernatants of cultured tumor cells over time, suggesting constant production and secretion. Correspondingly, as assessed by RT-PCR, primary tumor cells as well as the cell lines tested were found to express VEGF mRNA in a constitutive manner. Since mTOR is a well known regulator of VEGF synthesis, we applied rapamycin on primary neoplastic cells and on tumor cell lines. Rapamycin (20–200 nM) was found to counteract the production and secretion of VEGF in all tumor cells tested (VEGF in supernatants in cultures supplemented with rapamycin at 100 nM compared to control=100% on day 6: MDA-MB231: 11.8±0.2%; BxPC-3: 23.6±18.8%; A-427: 30.1±3.4%; HCT8 17.2±0.5%; EGI-1 28.4±1.1%; p<0.05). By contrast, neither rapamycin nor VEGF were found to modulate growth of primary tumor cells or the growth of the tumor cell lines tested. Conclusions: Various human tumor cells express and secrete VEGF. VEGF production is mediated through mTOR. These observations may have implications for the design of new treatment approaches attempting to counteract VEGF production/secretion and thus VEGF-dependent angiogenesis and effusion- formation in solid tumors. No significant financial relationships to disclose.


2013 ◽  
Vol 13 (10) ◽  
pp. 1582-1589 ◽  
Author(s):  
Cristiane Cazal ◽  
Kantima Choosang ◽  
Vanessa Severino ◽  
João Fernandes ◽  
Maria Silva ◽  
...  

2004 ◽  
Vol 67 (7) ◽  
pp. 1193-1196 ◽  
Author(s):  
Cristina Moiteiro ◽  
César Manta ◽  
Fátima Justino ◽  
Regina Tavares ◽  
Maria João M. Curto ◽  
...  

1982 ◽  
Vol 31 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
J. Balzarini ◽  
E. De Clercq ◽  
P.F. Torrenc ◽  
M.P. Mertes ◽  
J.S. Park ◽  
...  

ChemInform ◽  
2006 ◽  
Vol 37 (34) ◽  
Author(s):  
A. M. A. G. Oliveira ◽  
M. Manuela M. Raposo ◽  
A. M. F. Oliveira-Campos ◽  
A. E. H. Machado ◽  
Prapawadee Puapairoj ◽  
...  

2006 ◽  
Vol 41 (3) ◽  
pp. 367-372 ◽  
Author(s):  
A.M.A.G. Oliveira ◽  
M. Manuela M. Raposo ◽  
A.M.F. Oliveira-Campos ◽  
A.E.H. Machado ◽  
Prapawadee Puapairoj ◽  
...  

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