ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker
Background: Increases in expression of ADAM10 and ADAM17 genes and proteins are inconsistently found in cancer lesions, and are not validated as clinically useful biomarkers. The enzyme-specific proteolytic activities, which are solely mediated by the active mature enzymes, directly reflect enzyme c...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Ivyspring International Publisher
2018
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| Online Access: | http://hdl.handle.net/1721.1/117640 https://orcid.org/0000-0002-1801-5548 https://orcid.org/0000-0002-0050-989X |
| _version_ | 1826214204116303872 |
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| author | Yoneyama, Toshie Gorry, Michael Sobo-Vujanovic, Andrea Lin, Yan Vujanovic, Lazar Gaither-Davis, Autumn Moss, Marcia L. Stabile, Laura P. Herman, James Vujanovic, Nikola L. Miller, Miles Aaron Griffith, Linda G Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Biotechnology Process Engineering Center |
| author_facet | Massachusetts Institute of Technology. Biotechnology Process Engineering Center Yoneyama, Toshie Gorry, Michael Sobo-Vujanovic, Andrea Lin, Yan Vujanovic, Lazar Gaither-Davis, Autumn Moss, Marcia L. Stabile, Laura P. Herman, James Vujanovic, Nikola L. Miller, Miles Aaron Griffith, Linda G Lauffenburger, Douglas A |
| author_sort | Yoneyama, Toshie |
| collection | MIT |
| description | Background: Increases in expression of ADAM10 and ADAM17 genes and proteins are inconsistently found in cancer lesions, and are not validated as clinically useful biomarkers. The enzyme-specific proteolytic activities, which are solely mediated by the active mature enzymes, directly reflect enzyme cellular functions and might be superior biomarkers than the enzyme gene or protein expressions, which comprise the inactive proenzymes and active and inactivated mature enzymes. Methods: Using a recent modification of the proteolytic activity matrix analysis (PrAMA) measuring specific enzyme activities in cell and tissue lysates, we examined the specific sheddase activities of ADAM10 (ADAM10sa) and ADAM17 (ADAM17sa) in human non-small cell lung-carcinoma (NSCLC) cell lines, patient primary tumors and blood exosomes, and the noncancerous counterparts. Results: NSCLC cell lines and patient tumors and exosomes consistently showed significant increases of ADAM10sa relative to their normal, inflammatory and/or benign-tumor controls. Additionally, stage IA-IIB NSCLC primary tumors of patients who died of the disease exhibited greater increases of ADAM10sa than those of patients who survived 5 years following diagnosis and surgery. In contrast, NSCLC cell lines and patient tumors and exosomes did not display increases of ADAM17sa. Conclusions: This study is the first to investigate enzyme-specific proteolytic activities as potential cancer biomarkers. It provides a proof-of-concept that ADAM10sa could be a biomarker for NSCLC early detection and outcome prediction. To ascertain that ADAM10sa is a useful cancer biomarker, further robust clinical validation studies are needed. |
| first_indexed | 2024-09-23T16:01:25Z |
| format | Article |
| id | mit-1721.1/117640 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:01:25Z |
| publishDate | 2018 |
| publisher | Ivyspring International Publisher |
| record_format | dspace |
| spelling | mit-1721.1/1176402022-10-02T05:46:45Z ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker Yoneyama, Toshie Gorry, Michael Sobo-Vujanovic, Andrea Lin, Yan Vujanovic, Lazar Gaither-Davis, Autumn Moss, Marcia L. Stabile, Laura P. Herman, James Vujanovic, Nikola L. Miller, Miles Aaron Griffith, Linda G Lauffenburger, Douglas A Massachusetts Institute of Technology. Biotechnology Process Engineering Center Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Miller, Miles Aaron Griffith, Linda G Lauffenburger, Douglas A Background: Increases in expression of ADAM10 and ADAM17 genes and proteins are inconsistently found in cancer lesions, and are not validated as clinically useful biomarkers. The enzyme-specific proteolytic activities, which are solely mediated by the active mature enzymes, directly reflect enzyme cellular functions and might be superior biomarkers than the enzyme gene or protein expressions, which comprise the inactive proenzymes and active and inactivated mature enzymes. Methods: Using a recent modification of the proteolytic activity matrix analysis (PrAMA) measuring specific enzyme activities in cell and tissue lysates, we examined the specific sheddase activities of ADAM10 (ADAM10sa) and ADAM17 (ADAM17sa) in human non-small cell lung-carcinoma (NSCLC) cell lines, patient primary tumors and blood exosomes, and the noncancerous counterparts. Results: NSCLC cell lines and patient tumors and exosomes consistently showed significant increases of ADAM10sa relative to their normal, inflammatory and/or benign-tumor controls. Additionally, stage IA-IIB NSCLC primary tumors of patients who died of the disease exhibited greater increases of ADAM10sa than those of patients who survived 5 years following diagnosis and surgery. In contrast, NSCLC cell lines and patient tumors and exosomes did not display increases of ADAM17sa. Conclusions: This study is the first to investigate enzyme-specific proteolytic activities as potential cancer biomarkers. It provides a proof-of-concept that ADAM10sa could be a biomarker for NSCLC early detection and outcome prediction. To ascertain that ADAM10sa is a useful cancer biomarker, further robust clinical validation studies are needed. National Institutes of Health (U.S.) (R01 CA96504) 2018-09-05T16:13:56Z 2018-09-05T16:13:56Z 2018-06 2017-12 2018-08-30T17:08:32Z Article http://purl.org/eprint/type/JournalArticle 1837-9664 http://hdl.handle.net/1721.1/117640 Yoneyama, Toshie, Michael Gorry, Andrea Sobo-Vujanovic, Yan Lin, Lazar Vujanovic, Autumn Gaither-Davis, Marcia L. Moss, et al. “ADAM10 Sheddase Activity Is a Potential Lung-Cancer Biomarker.” Journal of Cancer 9, no. 14 (2018): 2559–2570. https://orcid.org/0000-0002-1801-5548 https://orcid.org/0000-0002-0050-989X http://dx.doi.org/10.7150/jca.24601 Journal of Cancer Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Ivyspring International Publisher Journal of Cancer |
| spellingShingle | Yoneyama, Toshie Gorry, Michael Sobo-Vujanovic, Andrea Lin, Yan Vujanovic, Lazar Gaither-Davis, Autumn Moss, Marcia L. Stabile, Laura P. Herman, James Vujanovic, Nikola L. Miller, Miles Aaron Griffith, Linda G Lauffenburger, Douglas A ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title | ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title_full | ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title_fullStr | ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title_full_unstemmed | ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title_short | ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker |
| title_sort | adam10 sheddase activity is a potential lung cancer biomarker |
| url | http://hdl.handle.net/1721.1/117640 https://orcid.org/0000-0002-1801-5548 https://orcid.org/0000-0002-0050-989X |
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