IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors
Abstract Background Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiologi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s10020-018-0003-z |
| _version_ | 1818041803383767040 |
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| author | A. Armakolas A. Dimakakos C. Loukogiannaki N. Armakolas A. Antonopoulos C. Florou P. Tsioli E. Papageorgiou T. P. Alexandrou M. Stathaki D. Spinos D. Pektasides E. Patsouris M. Koutsilieris |
| author_facet | A. Armakolas A. Dimakakos C. Loukogiannaki N. Armakolas A. Antonopoulos C. Florou P. Tsioli E. Papageorgiou T. P. Alexandrou M. Stathaki D. Spinos D. Pektasides E. Patsouris M. Koutsilieris |
| author_sort | A. Armakolas |
| collection | DOAJ |
| description | Abstract Background Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. Methods IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. Results We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. Conclusions IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair. |
| first_indexed | 2024-12-10T08:36:14Z |
| format | Article |
| id | doaj.art-9d66e000ce874674855b74fd0133fa6e |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-10T08:36:14Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-9d66e000ce874674855b74fd0133fa6e2022-12-22T01:55:58ZengBMCMolecular Medicine1076-15511528-36582018-03-0124111310.1186/s10020-018-0003-zIL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumorsA. Armakolas0A. Dimakakos1C. Loukogiannaki2N. Armakolas3A. Antonopoulos4C. Florou5P. Tsioli6E. Papageorgiou7T. P. Alexandrou8M. Stathaki9D. Spinos10D. Pektasides11E. Patsouris12M. Koutsilieris13Physiology Laboratory, Medical School, National & Kapodistrian University of AthensPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensThird orthopaedic clinic, KAT General HospitalThird orthopaedic clinic, KAT General HospitalOncology Section, Second Department of Internal Medicine, Hippokration HospitalDepartment of Pathology, University of Athens, Medical SchoolPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensDepartment of Pathology, University of Athens, Medical SchoolPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensOncology Section, Second Department of Internal Medicine, Hippokration HospitalDepartment of Pathology, University of Athens, Medical SchoolPhysiology Laboratory, Medical School, National & Kapodistrian University of AthensAbstract Background Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. Methods IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. Results We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. Conclusions IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair.http://link.springer.com/article/10.1186/s10020-018-0003-zImmune responseIGF-1EcIl-6Il-6RJAK2/STAT3 pathwayMSCs mobilisation |
| spellingShingle | A. Armakolas A. Dimakakos C. Loukogiannaki N. Armakolas A. Antonopoulos C. Florou P. Tsioli E. Papageorgiou T. P. Alexandrou M. Stathaki D. Spinos D. Pektasides E. Patsouris M. Koutsilieris IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors Molecular Medicine Immune response IGF-1Ec Il-6 Il-6R JAK2/STAT3 pathway MSCs mobilisation |
| title | IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors |
| title_full | IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors |
| title_fullStr | IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors |
| title_full_unstemmed | IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors |
| title_short | IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors |
| title_sort | il 6 is associated to igf 1ec upregulation and ec peptide secretion from prostate tumors |
| topic | Immune response IGF-1Ec Il-6 Il-6R JAK2/STAT3 pathway MSCs mobilisation |
| url | http://link.springer.com/article/10.1186/s10020-018-0003-z |
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