Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells
Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2015
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| Online Access: | http://hdl.handle.net/1721.1/96467 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7603-8396 |
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| author | Yao, Xiaosai Labelle, Myriam Lamb, Carla R. Dugan, John M. Williamson, Christina A. Spencer, Donna R. Christ, Kimberly R. Keating, Ryan O. Lee, W. David Paradis, Glenn A. Begum, Shahinoor Wittrup, Karl Dane Hynes, Richard O |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Yao, Xiaosai Labelle, Myriam Lamb, Carla R. Dugan, John M. Williamson, Christina A. Spencer, Donna R. Christ, Kimberly R. Keating, Ryan O. Lee, W. David Paradis, Glenn A. Begum, Shahinoor Wittrup, Karl Dane Hynes, Richard O |
| author_sort | Yao, Xiaosai |
| collection | MIT |
| description | Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10[superscript 3]–7 × 10[superscript 6] copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24[superscript high] tumor cells formed tumors in mice at a faster rate than CD24[superscript low] tumor cells, and shRNA-mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells. |
| first_indexed | 2024-09-23T12:56:49Z |
| format | Article |
| id | mit-1721.1/96467 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:56:49Z |
| publishDate | 2015 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/964672022-09-28T11:02:04Z Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells Yao, Xiaosai Labelle, Myriam Lamb, Carla R. Dugan, John M. Williamson, Christina A. Spencer, Donna R. Christ, Kimberly R. Keating, Ryan O. Lee, W. David Paradis, Glenn A. Begum, Shahinoor Wittrup, Karl Dane Hynes, Richard O Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Labelle, Myriam Yao, Xiaosai Keating, Ryan O. Lee, W. David Paradis, Glenn A. Begum, Shahinoor Hynes, Richard O. Wittrup, Karl Dane Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10[superscript 3]–7 × 10[superscript 6] copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24[superscript high] tumor cells formed tumors in mice at a faster rate than CD24[superscript low] tumor cells, and shRNA-mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells. 2015-04-08T18:40:01Z 2015-04-08T18:40:01Z 2013-07 2013-03 Article http://purl.org/eprint/type/JournalArticle 00207136 1097-0215 http://hdl.handle.net/1721.1/96467 Yao, Xiaosai, Myriam Labelle, Carla R. Lamb, John M. Dugan, Christina A. Williamson, Donna R. Spencer, Kimberly R. Christ, et al. “Determination of 35 Cell Surface Antigen Levels in Malignant Pleural Effusions Identifies CD24 as a Marker of Disseminated Tumor Cells.” Int. J. Cancer (June 2013). https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7603-8396 en_US http://dx.doi.org/10.1002/ijc.28312 International Journal of Cancer Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Yao, Xiaosai Labelle, Myriam Lamb, Carla R. Dugan, John M. Williamson, Christina A. Spencer, Donna R. Christ, Kimberly R. Keating, Ryan O. Lee, W. David Paradis, Glenn A. Begum, Shahinoor Wittrup, Karl Dane Hynes, Richard O Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title | Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title_full | Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title_fullStr | Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title_full_unstemmed | Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title_short | Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells |
| title_sort | determination of 35 cell surface antigen levels in malignant pleural effusions identifies cd24 as a marker of disseminated tumor cells |
| url | http://hdl.handle.net/1721.1/96467 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7603-8396 |
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