Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients
Abstract Cell lines derived from circulating tumor cells (CTCs) in the blood provide important biological information on cancer metastasis. CTC-ITB-01 is a CTC cell line derived from a patient with metastatic estrogen receptor-alpha (ER-alpha) positive breast cancer two months before the death of th...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87122-4 |
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| author | Kai Bartkowiak Parinaz Mossahebi Mohammadi Paula Nissen Stefan Werner David Agorku Antje Andreas Maria Geffken Sven Peine Karl Verpoort Thomas M. Deutsch Laura L. Michel Andreas Schneeweiss Verena Thewes Andreas Trumpp Olaf Hardt Volkmar Müller Sabine Riethdorf Hartmut Schlüter Klaus Pantel |
| author_facet | Kai Bartkowiak Parinaz Mossahebi Mohammadi Paula Nissen Stefan Werner David Agorku Antje Andreas Maria Geffken Sven Peine Karl Verpoort Thomas M. Deutsch Laura L. Michel Andreas Schneeweiss Verena Thewes Andreas Trumpp Olaf Hardt Volkmar Müller Sabine Riethdorf Hartmut Schlüter Klaus Pantel |
| author_sort | Kai Bartkowiak |
| collection | DOAJ |
| description | Abstract Cell lines derived from circulating tumor cells (CTCs) in the blood provide important biological information on cancer metastasis. CTC-ITB-01 is a CTC cell line derived from a patient with metastatic estrogen receptor-alpha (ER-alpha) positive breast cancer two months before the death of the patient. After a LC-MC/MS based proteomics analysis of CTC-ITB-01, we found extraordinary high levels of the poorly characterized protein SUSD2 (sushi domain-containing protein 2) in CTC-ITB-01. Expression of SUSD2 on subsets of CTCs was validated on clinical blood samples of patients with metastatic breast cancer. SUSD2-positive CTCs could be captured specifically by a MACS-based approach. We overexpressed SUSD2 in the poorly-metastatic cell line MCF-7. This resulted in upregulation of ER-alpha, the tumor progression protein GRP78 (78-kDa glucose-regulated protein) and downregulation of the tumor suppressor protein PDCD4 (programmed cell death protein 4). We observed downregulation of SUSD2 and PDCD4 after hypoxia and simulation of re-oxygenation in the blood in MCF-7 and MDA-MB-468, while in CTC-ITB-01 SUSD2 levels remained unchanged, and only PDCD4 was downregulated under hypoxia. In conclusion, we show, for the first time, that SUSD2 is expressed in CTCs and appears to affect key proteins in tumor progression and survival. |
| format | Article |
| id | doaj-art-f70490ad16ef4ae3ad11756a6f07005c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f70490ad16ef4ae3ad11756a6f07005c2025-02-02T12:23:50ZengNature PortfolioScientific Reports2045-23222025-01-0115111810.1038/s41598-025-87122-4Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patientsKai Bartkowiak0Parinaz Mossahebi Mohammadi1Paula Nissen2Stefan Werner3David Agorku4Antje Andreas5Maria Geffken6Sven Peine7Karl Verpoort8Thomas M. Deutsch9Laura L. Michel10Andreas Schneeweiss11Verena Thewes12Andreas Trumpp13Olaf Hardt14Volkmar Müller15Sabine Riethdorf16Hartmut Schlüter17Klaus Pantel18Department for Tumour Biology, University Medical Centre Hamburg-EppendorfDepartment for Tumour Biology, University Medical Centre Hamburg-EppendorfSection Mass Spectrometry and Proteomics, University Medical Centre Hamburg-EppendorfDepartment for Tumour Biology, University Medical Centre Hamburg-EppendorfMiltenyi Biotec B.V. & Co. KGDepartment for Tumour Biology, University Medical Centre Hamburg-EppendorfDepartment of Transfusion Medicine, University Medical Centre Hamburg-EppendorfDepartment of Transfusion Medicine, University Medical Centre Hamburg-EppendorfSuperregional group practice for hematology and oncologyDepartment of Obstetrics and Gynecology, University of HeidelbergNational Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research CenterNational Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research CenterDivision of Molecular Genetics, German Cancer Research Center (DKFZ)Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ- ZMBH AllianceMiltenyi Biotec B.V. & Co. KGDepartment of Gynecology, University Medical Center Hamburg-EppendorfDepartment for Tumour Biology, University Medical Centre Hamburg-EppendorfSection Mass Spectrometry and Proteomics, University Medical Centre Hamburg-EppendorfDepartment for Tumour Biology, University Medical Centre Hamburg-EppendorfAbstract Cell lines derived from circulating tumor cells (CTCs) in the blood provide important biological information on cancer metastasis. CTC-ITB-01 is a CTC cell line derived from a patient with metastatic estrogen receptor-alpha (ER-alpha) positive breast cancer two months before the death of the patient. After a LC-MC/MS based proteomics analysis of CTC-ITB-01, we found extraordinary high levels of the poorly characterized protein SUSD2 (sushi domain-containing protein 2) in CTC-ITB-01. Expression of SUSD2 on subsets of CTCs was validated on clinical blood samples of patients with metastatic breast cancer. SUSD2-positive CTCs could be captured specifically by a MACS-based approach. We overexpressed SUSD2 in the poorly-metastatic cell line MCF-7. This resulted in upregulation of ER-alpha, the tumor progression protein GRP78 (78-kDa glucose-regulated protein) and downregulation of the tumor suppressor protein PDCD4 (programmed cell death protein 4). We observed downregulation of SUSD2 and PDCD4 after hypoxia and simulation of re-oxygenation in the blood in MCF-7 and MDA-MB-468, while in CTC-ITB-01 SUSD2 levels remained unchanged, and only PDCD4 was downregulated under hypoxia. In conclusion, we show, for the first time, that SUSD2 is expressed in CTCs and appears to affect key proteins in tumor progression and survival.https://doi.org/10.1038/s41598-025-87122-4SUSD2Breast cancerCirculating tumor cellsEstrogen receptor positiveMetastasisPDCD4 |
| spellingShingle | Kai Bartkowiak Parinaz Mossahebi Mohammadi Paula Nissen Stefan Werner David Agorku Antje Andreas Maria Geffken Sven Peine Karl Verpoort Thomas M. Deutsch Laura L. Michel Andreas Schneeweiss Verena Thewes Andreas Trumpp Olaf Hardt Volkmar Müller Sabine Riethdorf Hartmut Schlüter Klaus Pantel Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients Scientific Reports SUSD2 Breast cancer Circulating tumor cells Estrogen receptor positive Metastasis PDCD4 |
| title | Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| title_full | Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| title_fullStr | Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| title_full_unstemmed | Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| title_short | Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| title_sort | discovery of a sushi domain containing protein 2 positive phenotype in circulating tumor cells of metastatic breast cancer patients |
| topic | SUSD2 Breast cancer Circulating tumor cells Estrogen receptor positive Metastasis PDCD4 |
| url | https://doi.org/10.1038/s41598-025-87122-4 |
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