Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration
Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epi...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/96394 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826190131020693504 |
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| author | Gertler, Frank Pignatelli, Jeanine Goswami, Sumanta Jones, Joan G. Rohan, Thomas E. Pieri, Evan Chen, Xiaoming Adler, Esther Cox, Dianne Maleki, Sara Bresnick, Anne Condeelis, John S. Oktay, Maja H. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gertler, Frank Pignatelli, Jeanine Goswami, Sumanta Jones, Joan G. Rohan, Thomas E. Pieri, Evan Chen, Xiaoming Adler, Esther Cox, Dianne Maleki, Sara Bresnick, Anne Condeelis, John S. Oktay, Maja H. |
| author_sort | Gertler, Frank |
| collection | MIT |
| description | Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)–responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena[superscript INV], an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena[superscript INV] or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena[superscript INV] and TMEM frequency are correlated prognostic markers and CSF-1 and Mena[superscript INV] may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. |
| first_indexed | 2024-09-23T08:35:30Z |
| format | Article |
| id | mit-1721.1/96394 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:35:30Z |
| publishDate | 2015 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/963942022-09-23T13:06:56Z Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration Gertler, Frank Pignatelli, Jeanine Goswami, Sumanta Jones, Joan G. Rohan, Thomas E. Pieri, Evan Chen, Xiaoming Adler, Esther Cox, Dianne Maleki, Sara Bresnick, Anne Condeelis, John S. Oktay, Maja H. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gertler, Frank Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)–responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena[superscript INV], an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena[superscript INV] or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena[superscript INV] and TMEM frequency are correlated prognostic markers and CSF-1 and Mena[superscript INV] may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. 2015-04-07T16:41:20Z 2015-04-07T16:41:20Z 2014-11 2014-03 Article http://purl.org/eprint/type/JournalArticle 1945-0877 1937-9145 http://hdl.handle.net/1721.1/96394 Pignatelli, J., S. Goswami, J. G. Jones, T. E. Rohan, E. Pieri, X. Chen, E. Adler, et al. “Invasive Breast Carcinoma Cells from Patients Exhibit Mena[superscript INV]- and Macrophage-Dependent Transendothelial Migration.” Science Signaling 7, no. 353 (November 25, 2014): ra112–ra112. © 2014 American Association for the Advancement of Science https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1126/scisignal.2005329 Science Signaling Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Gertler, Frank Pignatelli, Jeanine Goswami, Sumanta Jones, Joan G. Rohan, Thomas E. Pieri, Evan Chen, Xiaoming Adler, Esther Cox, Dianne Maleki, Sara Bresnick, Anne Condeelis, John S. Oktay, Maja H. Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title | Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title_full | Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title_fullStr | Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title_full_unstemmed | Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title_short | Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration |
| title_sort | invasive breast carcinoma cells from patients exhibit mena superscript inv and macrophage dependent transendothelial migration |
| url | http://hdl.handle.net/1721.1/96394 https://orcid.org/0000-0003-3214-4554 |
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