A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages
The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that t...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Springer Nature
2018
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| Online Access: | http://hdl.handle.net/1721.1/116951 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826205173622505472 |
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| author | Clauser, Karl R. Fröse, Julia Ye, Xin Eaton, Elinor Ng Reinhardt, Ferenc Donnenberg, Vera S. Bhargava, Rohit Carr, Steven A. Lu, Haihui Tam, Wai Leong Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Clauser, Karl R. Fröse, Julia Ye, Xin Eaton, Elinor Ng Reinhardt, Ferenc Donnenberg, Vera S. Bhargava, Rohit Carr, Steven A. Lu, Haihui Tam, Wai Leong Weinberg, Robert A |
| author_sort | Clauser, Karl R. |
| collection | MIT |
| description | The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that tumour-associated monocytes and macrophages (TAMs) create a CSC niche through juxtacrine signalling with CSCs. We performed quantitative proteomic profiling and found that the EMT program upregulates the expression of CD90, also known as Thy1, and EphA4, which mediate the physical interactions of CSCs with TAMs by directly binding with their respective counter-receptors on these cells. In response, the EphA4 receptor on the carcinoma cells activates Src and NF-κ B. In turn, NF-κ B in the CSCs induces the secretion of a variety of cytokines that serve to sustain the stem cell state. Indeed, admixed macrophages enhance the CSC activities of carcinoma cells. These findings underscore the significance of TAMs as important components of the CSC niche. |
| first_indexed | 2024-09-23T13:08:53Z |
| format | Article |
| id | mit-1721.1/116951 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:08:53Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1169512022-10-01T13:18:44Z A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages Clauser, Karl R. Fröse, Julia Ye, Xin Eaton, Elinor Ng Reinhardt, Ferenc Donnenberg, Vera S. Bhargava, Rohit Carr, Steven A. Lu, Haihui Tam, Wai Leong Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) Lu, Haihui Tam, Wai Leong Weinberg, Robert A The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that tumour-associated monocytes and macrophages (TAMs) create a CSC niche through juxtacrine signalling with CSCs. We performed quantitative proteomic profiling and found that the EMT program upregulates the expression of CD90, also known as Thy1, and EphA4, which mediate the physical interactions of CSCs with TAMs by directly binding with their respective counter-receptors on these cells. In response, the EphA4 receptor on the carcinoma cells activates Src and NF-κ B. In turn, NF-κ B in the CSCs induces the secretion of a variety of cytokines that serve to sustain the stem cell state. Indeed, admixed macrophages enhance the CSC activities of carcinoma cells. These findings underscore the significance of TAMs as important components of the CSC niche. National Institutes of Health (U.S.) (Grant R01-CA078461) National Institutes of Health (U.S.) (Grant P01-CA080111) National Institutes of Health (U.S.) (Grant U54-CA163109) 2018-07-12T19:16:53Z 2018-07-12T19:16:53Z 2014-09 2014-07 2018-07-12T17:13:05Z Article http://purl.org/eprint/type/JournalArticle 1465-7392 1476-4679 http://hdl.handle.net/1721.1/116951 Lu, Haihui et al. “A Breast Cancer Stem Cell Niche Supported by Juxtacrine Signalling from Monocytes and Macrophages.” Nature Cell Biology 16, 11 (September 2014): 1105–1117 © 2014 Macmillan Publishers Limited https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1038/NCB3041 Nature Cell Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Nature PMC |
| spellingShingle | Clauser, Karl R. Fröse, Julia Ye, Xin Eaton, Elinor Ng Reinhardt, Ferenc Donnenberg, Vera S. Bhargava, Rohit Carr, Steven A. Lu, Haihui Tam, Wai Leong Weinberg, Robert A A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title | A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title_full | A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title_fullStr | A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title_full_unstemmed | A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title_short | A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| title_sort | breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages |
| url | http://hdl.handle.net/1721.1/116951 https://orcid.org/0000-0002-0895-3557 |
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