Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines
Small cell lung cancer (SCLC) is an aggressive type of lung cancer which disseminates vigorously and has a dismal prognosis. Metastasis of SCLC is linked to an extremely high number of circulating tumor cells (CTCs), which form chemoresistant spheroids, termed tumorospheres. Intravasation and extrav...
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| Format: | Article |
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MDPI AG
2019-01-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/11/1/114 |
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| author | Barbara Rath Lukas Klameth Adelina Plangger Maximilian Hochmair Ernst Ulsperger Ihor Huk Robert Zeillinger Gerhard Hamilton |
| author_facet | Barbara Rath Lukas Klameth Adelina Plangger Maximilian Hochmair Ernst Ulsperger Ihor Huk Robert Zeillinger Gerhard Hamilton |
| author_sort | Barbara Rath |
| collection | DOAJ |
| description | Small cell lung cancer (SCLC) is an aggressive type of lung cancer which disseminates vigorously and has a dismal prognosis. Metastasis of SCLC is linked to an extremely high number of circulating tumor cells (CTCs), which form chemoresistant spheroids, termed tumorospheres. Intravasation and extravasation during tumor spread requires the activity of a number of proteases to disintegrate the stroma and vascular tissue. Generation of several permanent SCLC CTC lines allowed us to screen for the expression of 35 proteases using Western blot arrays. Cell culture supernatants of two CTC lines, namely BHGc7 and 10, were analyzed for secreted proteases, including matrix metalloproteinases (MMPs), ADAM/TS, cathepsins, kallikreins, and others, and compared to proteases expressed by SCLC cell lines (GLC14, GLC16, NCI-H526 and SCLC26A). In contrast to NCI-H526 and SCLC26A, MMP-9 was highly expressed in the two CTC lines and in GLC16 derived of a relapse. Furthermore, cathepsins (S, V, X/Z/P, A and D) were highly expressed in the CTC lines, whereas ADAM/TS and kallikreins were not detectable. In conclusion, SCLC CTCs express MMP-9 and a range of cathepsins for proteolysis and, aside from tissue degradation, these enzymes are involved in cell signaling, survival, and the chemoresistance of tumor cells. |
| first_indexed | 2024-03-12T11:14:34Z |
| format | Article |
| id | doaj.art-3fd53fa8f1d34439b9d0edb99b7a88b9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T11:14:34Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3fd53fa8f1d34439b9d0edb99b7a88b92023-09-02T02:16:41ZengMDPI AGCancers2072-66942019-01-0111111410.3390/cancers11010114cancers11010114Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell LinesBarbara Rath0Lukas Klameth1Adelina Plangger2Maximilian Hochmair3Ernst Ulsperger4Ihor Huk5Robert Zeillinger6Gerhard Hamilton7Department of Vascular Surgery, Medical University of Vienna, A-1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, AustriaDepartment of Vascular Surgery, Medical University of Vienna, A-1090 Vienna, AustriaRespiratory Oncology Unit, Otto Wagner Hospital, A-1140 Vienna, AustriaHospital Horn, A-3580 Horn, AustriaDepartment of Vascular Surgery, Medical University of Vienna, A-1090 Vienna, AustriaMolecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecological Cancer Unit, Medical University of Vienna, A-1090 Vienna, AustriaDepartment of Vascular Surgery, Medical University of Vienna, A-1090 Vienna, AustriaSmall cell lung cancer (SCLC) is an aggressive type of lung cancer which disseminates vigorously and has a dismal prognosis. Metastasis of SCLC is linked to an extremely high number of circulating tumor cells (CTCs), which form chemoresistant spheroids, termed tumorospheres. Intravasation and extravasation during tumor spread requires the activity of a number of proteases to disintegrate the stroma and vascular tissue. Generation of several permanent SCLC CTC lines allowed us to screen for the expression of 35 proteases using Western blot arrays. Cell culture supernatants of two CTC lines, namely BHGc7 and 10, were analyzed for secreted proteases, including matrix metalloproteinases (MMPs), ADAM/TS, cathepsins, kallikreins, and others, and compared to proteases expressed by SCLC cell lines (GLC14, GLC16, NCI-H526 and SCLC26A). In contrast to NCI-H526 and SCLC26A, MMP-9 was highly expressed in the two CTC lines and in GLC16 derived of a relapse. Furthermore, cathepsins (S, V, X/Z/P, A and D) were highly expressed in the CTC lines, whereas ADAM/TS and kallikreins were not detectable. In conclusion, SCLC CTCs express MMP-9 and a range of cathepsins for proteolysis and, aside from tissue degradation, these enzymes are involved in cell signaling, survival, and the chemoresistance of tumor cells.http://www.mdpi.com/2072-6694/11/1/114small cell lung cancercirculating tumor cellsproteasesMMP-9cathepsin Smetastasis |
| spellingShingle | Barbara Rath Lukas Klameth Adelina Plangger Maximilian Hochmair Ernst Ulsperger Ihor Huk Robert Zeillinger Gerhard Hamilton Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines Cancers small cell lung cancer circulating tumor cells proteases MMP-9 cathepsin S metastasis |
| title | Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines |
| title_full | Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines |
| title_fullStr | Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines |
| title_full_unstemmed | Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines |
| title_short | Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines |
| title_sort | expression of proteolytic enzymes by small cell lung cancer circulating tumor cell lines |
| topic | small cell lung cancer circulating tumor cells proteases MMP-9 cathepsin S metastasis |
| url | http://www.mdpi.com/2072-6694/11/1/114 |
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