Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression

Although treatment options in breast cancer have been improved significantly, predictive biomarkers for disease progression and metastasis are still lacking. Recent studies indicate that several TNF Receptor Superfamily members are involved in breast cancer cell proliferation and survival. Interesti...

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Main Authors: Clemens Hinterleitner, Yanjun Zhou, Claudia Tandler, Jonas S. Heitmann, Korbinian N. Kropp, Martina Hinterleitner, André Koch, Andreas D. Hartkopf, Lars Zender, Helmut R. Salih, Stefanie Maurer
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.642170/full
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author Clemens Hinterleitner
Clemens Hinterleitner
Yanjun Zhou
Yanjun Zhou
Claudia Tandler
Claudia Tandler
Jonas S. Heitmann
Jonas S. Heitmann
Korbinian N. Kropp
Martina Hinterleitner
Martina Hinterleitner
André Koch
Andreas D. Hartkopf
Lars Zender
Lars Zender
Lars Zender
Helmut R. Salih
Helmut R. Salih
Stefanie Maurer
Stefanie Maurer
Stefanie Maurer
author_facet Clemens Hinterleitner
Clemens Hinterleitner
Yanjun Zhou
Yanjun Zhou
Claudia Tandler
Claudia Tandler
Jonas S. Heitmann
Jonas S. Heitmann
Korbinian N. Kropp
Martina Hinterleitner
Martina Hinterleitner
André Koch
Andreas D. Hartkopf
Lars Zender
Lars Zender
Lars Zender
Helmut R. Salih
Helmut R. Salih
Stefanie Maurer
Stefanie Maurer
Stefanie Maurer
author_sort Clemens Hinterleitner
collection DOAJ
description Although treatment options in breast cancer have been improved significantly, predictive biomarkers for disease progression and metastasis are still lacking. Recent studies indicate that several TNF Receptor Superfamily members are involved in breast cancer cell proliferation and survival. Interestingly, TNFRSF13B (TACI) mRNA level were of prognostic relevance in breast cancer patients. In this study we provide evidence for TACI expression on platelets of breast cancer patients. The level of platelet-expressed TACI (pTACI) was significantly increased on platelets derived from breast cancer patients compared to healthy controls. Upon platelet activation, pTACI was downregulated on the platelet surface of healthy donors and breast cancer patients. Of note, inhibition of matrix metalloprotease (MMP) prevented downregulation of pTACI ex vivo, indicating that proteolytic cleavage of pTACI is responsible for reduction of pTACI level. Stimulation of pTACI via BAFF, BAFF 60-mer or APRIL did not influence platelet activation and function. Remarkably, pTACI was particularly regulated during tumor progression in our breast cancer cohort. TACI expression levels on platelets were correlated with clinical parameters including tumor stage, occurrence of metastasis and tumor cell proliferation (Ki67). In conclusion, our data emphasize the potential use of platelets as a liquid biomarker in breast cancer.
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spelling doaj.art-f1e066b6d9144fb291563d5bed57ea7b2022-12-21T21:55:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.642170642170Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer ProgressionClemens Hinterleitner0Clemens Hinterleitner1Yanjun Zhou2Yanjun Zhou3Claudia Tandler4Claudia Tandler5Jonas S. Heitmann6Jonas S. Heitmann7Korbinian N. Kropp8Martina Hinterleitner9Martina Hinterleitner10André Koch11Andreas D. Hartkopf12Lars Zender13Lars Zender14Lars Zender15Helmut R. Salih16Helmut R. Salih17Stefanie Maurer18Stefanie Maurer19Stefanie Maurer20Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, GermanyDepartment of Hematology, Medical Oncology and Pneumology, University Medical Center of Mainz, Mainz, GermanyDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyDepartment of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, GermanyDepartment of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, GermanyDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyGerman Cancer Research Consortium (DKTK), Partner Site Tübingen, German Cancer Research Center (DKFZ), Heidelberg, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, GermanyCluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, GermanyDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesAlthough treatment options in breast cancer have been improved significantly, predictive biomarkers for disease progression and metastasis are still lacking. Recent studies indicate that several TNF Receptor Superfamily members are involved in breast cancer cell proliferation and survival. Interestingly, TNFRSF13B (TACI) mRNA level were of prognostic relevance in breast cancer patients. In this study we provide evidence for TACI expression on platelets of breast cancer patients. The level of platelet-expressed TACI (pTACI) was significantly increased on platelets derived from breast cancer patients compared to healthy controls. Upon platelet activation, pTACI was downregulated on the platelet surface of healthy donors and breast cancer patients. Of note, inhibition of matrix metalloprotease (MMP) prevented downregulation of pTACI ex vivo, indicating that proteolytic cleavage of pTACI is responsible for reduction of pTACI level. Stimulation of pTACI via BAFF, BAFF 60-mer or APRIL did not influence platelet activation and function. Remarkably, pTACI was particularly regulated during tumor progression in our breast cancer cohort. TACI expression levels on platelets were correlated with clinical parameters including tumor stage, occurrence of metastasis and tumor cell proliferation (Ki67). In conclusion, our data emphasize the potential use of platelets as a liquid biomarker in breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.642170/fullbreast cancerplateletsbiomarkermetastasisTACI/TNFRSF13Bcancer
spellingShingle Clemens Hinterleitner
Clemens Hinterleitner
Yanjun Zhou
Yanjun Zhou
Claudia Tandler
Claudia Tandler
Jonas S. Heitmann
Jonas S. Heitmann
Korbinian N. Kropp
Martina Hinterleitner
Martina Hinterleitner
André Koch
Andreas D. Hartkopf
Lars Zender
Lars Zender
Lars Zender
Helmut R. Salih
Helmut R. Salih
Stefanie Maurer
Stefanie Maurer
Stefanie Maurer
Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
Frontiers in Oncology
breast cancer
platelets
biomarker
metastasis
TACI/TNFRSF13B
cancer
title Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
title_full Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
title_fullStr Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
title_full_unstemmed Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
title_short Platelet-Expressed TNFRSF13B (TACI) Predicts Breast Cancer Progression
title_sort platelet expressed tnfrsf13b taci predicts breast cancer progression
topic breast cancer
platelets
biomarker
metastasis
TACI/TNFRSF13B
cancer
url https://www.frontiersin.org/articles/10.3389/fonc.2021.642170/full
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