MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas
Improved biomarkers are needed for vestibular schwannoma (VS), the most common tumor of the cerebellopontine angle, as existing clinical biomarkers have poor predictive value. Factors such as tumor size or growth rate do not shed light on the pathophysiology of associated sensorineural hearing loss...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00191/full |
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| author | Yin Ren Yin Ren Yin Ren Hiroshi Hyakusoku Hiroshi Hyakusoku Hiroshi Hyakusoku Jessica E. Sagers Jessica E. Sagers Jessica E. Sagers Lukas D. Landegger Lukas D. Landegger D. Bradley Welling D. Bradley Welling D. Bradley Welling Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic |
| author_facet | Yin Ren Yin Ren Yin Ren Hiroshi Hyakusoku Hiroshi Hyakusoku Hiroshi Hyakusoku Jessica E. Sagers Jessica E. Sagers Jessica E. Sagers Lukas D. Landegger Lukas D. Landegger D. Bradley Welling D. Bradley Welling D. Bradley Welling Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic |
| author_sort | Yin Ren |
| collection | DOAJ |
| description | Improved biomarkers are needed for vestibular schwannoma (VS), the most common tumor of the cerebellopontine angle, as existing clinical biomarkers have poor predictive value. Factors such as tumor size or growth rate do not shed light on the pathophysiology of associated sensorineural hearing loss (SNHL) and suffer from low specificity and sensitivity, whereas histological markers only sample a fraction of the tumor and are difficult to ascertain before tumor treatment or surgical intervention. Proteases play diverse and critical roles in tumorigenesis and could be leveraged as a new class of VS biomarkers. Using a combination of in silico, in vitro, and ex vivo approaches, we identified matrixmetalloprotease 14 (MMP-14; also known as MT1-MMP), from a panel of candidate proteases that were differentially expressed through the largest meta-analysis of human VS transcriptomes. The abundance and proteolytic activity of MMP-14 in the plasma and tumor secretions from VS patients correlated with clinical parameters and the degree of SNHL. Further, MMP-14 plasma levels correlated with surgical outcomes such as the extent of resection. Finally, the application of MMP-14 at physiologic concentrations to cochlear explant cultures led to damage to spiral ganglion neuronal fibers and synapses, thereby providing mechanistic insight into VS-associated SNHL. Taken together, MMP-14 represents a novel molecular biomarker that merits further validation in both diagnostic and prognostic applications for VS. |
| first_indexed | 2024-12-21T20:30:44Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-21T20:30:44Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-b0e2f14cbbef47dbbca520e3fa5aad2e2022-12-21T18:51:14ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-07-011410.3389/fncel.2020.00191537424MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular SchwannomasYin Ren0Yin Ren1Yin Ren2Hiroshi Hyakusoku3Hiroshi Hyakusoku4Hiroshi Hyakusoku5Jessica E. Sagers6Jessica E. Sagers7Jessica E. Sagers8Lukas D. Landegger9Lukas D. Landegger10D. Bradley Welling11D. Bradley Welling12D. Bradley Welling13Konstantina M. Stankovic14Konstantina M. Stankovic15Konstantina M. Stankovic16Konstantina M. Stankovic17Eaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesDivision of Otolaryngology—Head and Neck Surgery, University of California, San Diego, San Diego, CA, United StatesEaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesDepartment of Otorhinolaryngology, Yokosuka Kyosai Hospital, Kanagawa, JapanEaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesProgram in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, United StatesHarvard Program in Therapeutic Science, Harvard University, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesProgram in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesProgram in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, United StatesHarvard Program in Therapeutic Science, Harvard University, Boston, MA, United StatesImproved biomarkers are needed for vestibular schwannoma (VS), the most common tumor of the cerebellopontine angle, as existing clinical biomarkers have poor predictive value. Factors such as tumor size or growth rate do not shed light on the pathophysiology of associated sensorineural hearing loss (SNHL) and suffer from low specificity and sensitivity, whereas histological markers only sample a fraction of the tumor and are difficult to ascertain before tumor treatment or surgical intervention. Proteases play diverse and critical roles in tumorigenesis and could be leveraged as a new class of VS biomarkers. Using a combination of in silico, in vitro, and ex vivo approaches, we identified matrixmetalloprotease 14 (MMP-14; also known as MT1-MMP), from a panel of candidate proteases that were differentially expressed through the largest meta-analysis of human VS transcriptomes. The abundance and proteolytic activity of MMP-14 in the plasma and tumor secretions from VS patients correlated with clinical parameters and the degree of SNHL. Further, MMP-14 plasma levels correlated with surgical outcomes such as the extent of resection. Finally, the application of MMP-14 at physiologic concentrations to cochlear explant cultures led to damage to spiral ganglion neuronal fibers and synapses, thereby providing mechanistic insight into VS-associated SNHL. Taken together, MMP-14 represents a novel molecular biomarker that merits further validation in both diagnostic and prognostic applications for VS.https://www.frontiersin.org/article/10.3389/fncel.2020.00191/fullMMP-14vestibular schwannomabiomarkerhearing losssurgical outcome |
| spellingShingle | Yin Ren Yin Ren Yin Ren Hiroshi Hyakusoku Hiroshi Hyakusoku Hiroshi Hyakusoku Jessica E. Sagers Jessica E. Sagers Jessica E. Sagers Lukas D. Landegger Lukas D. Landegger D. Bradley Welling D. Bradley Welling D. Bradley Welling Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas Frontiers in Cellular Neuroscience MMP-14 vestibular schwannoma biomarker hearing loss surgical outcome |
| title | MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas |
| title_full | MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas |
| title_fullStr | MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas |
| title_full_unstemmed | MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas |
| title_short | MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas |
| title_sort | mmp 14 mt1 mmp is a biomarker of surgical outcome and a potential mediator of hearing loss in patients with vestibular schwannomas |
| topic | MMP-14 vestibular schwannoma biomarker hearing loss surgical outcome |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00191/full |
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