Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa
Summary Cancer patients are known to be highly susceptible to Pseudomonas aeruginosa (Pa) infection, but it remains unknown whether alterations at the tumor cell level can contribute to infection. This study explored how cellular changes associated with tumor metastasis influence Pa infection using...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2013-07-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/2/9/891 |
| _version_ | 1818734464246743040 |
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| author | Matthew J. Novotny Dacie R. Bridge Karen H. Martin Scott A. Weed Robert B. Wysolmerski Joan C. Olson |
| author_facet | Matthew J. Novotny Dacie R. Bridge Karen H. Martin Scott A. Weed Robert B. Wysolmerski Joan C. Olson |
| author_sort | Matthew J. Novotny |
| collection | DOAJ |
| description | Summary
Cancer patients are known to be highly susceptible to Pseudomonas aeruginosa (Pa) infection, but it remains unknown whether alterations at the tumor cell level can contribute to infection. This study explored how cellular changes associated with tumor metastasis influence Pa infection using highly metastatic MTLn3 cells and non-metastatic MTC cells as cell culture models. MTLn3 cells were found to be more sensitive to Pa infection than MTC cells based on increased translocation of the type III secretion effector, ExoS, into MTLn3 cells. Subsequent studies found that higher levels of ExoS translocation into MTLn3 cells related to Pa entry and secretion of ExoS within MTLn3 cells, rather than conventional ExoS translocation by external Pa. ExoS includes both Rho GTPase activating protein (GAP) and ADP-ribosyltransferase (ADPRT) enzyme activities, and differences in MTLn3 and MTC cell responsiveness to ExoS were found to relate to the targeting of ExoS-GAP activity to Rho GTPases. MTLn3 cell migration is mediated by RhoA activation at the leading edge, and inhibition of RhoA activity decreased ExoS translocation into MTLn3 cells to levels similar to those of MTC cells. The ability of Pa to be internalized and transfer ExoS more efficiently in association with Rho activation during tumor metastasis confirms that alterations in cell migration that occur in conjunction with tumor metastasis contribute to Pa infection in cancer patients. This study also raises the possibility that Pa might serve as a biological tool for dissecting or detecting cellular alterations associated with tumor metastasis. |
| first_indexed | 2024-12-18T00:05:46Z |
| format | Article |
| id | doaj.art-ec074df46c454e85a8a9632009d0ec68 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-18T00:05:46Z |
| publishDate | 2013-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-ec074df46c454e85a8a9632009d0ec682022-12-21T21:27:48ZengThe Company of BiologistsBiology Open2046-63902013-07-012989190010.1242/bio.2013363220133632Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosaMatthew J. Novotny0Dacie R. Bridge1Karen H. Martin2Scott A. Weed3Robert B. Wysolmerski4Joan C. Olson5 Department of Microbiology, Immunology and Cell Biology, West Virginia University Health Sciences Center, Morgantown, WV 26506-9177, USA Department of Microbiology, Immunology and Cell Biology, West Virginia University Health Sciences Center, Morgantown, WV 26506-9177, USA Department of Microbiology, Immunology and Cell Biology, West Virginia University Health Sciences Center, Morgantown, WV 26506-9177, USA Department of Neurobiology and Anatomy, West Virginia University Health Sciences Center, Morgantown, WV 26506-9128, USA Department of Neurobiology and Anatomy, West Virginia University Health Sciences Center, Morgantown, WV 26506-9128, USA Department of Microbiology, Immunology and Cell Biology, West Virginia University Health Sciences Center, Morgantown, WV 26506-9177, USA Summary Cancer patients are known to be highly susceptible to Pseudomonas aeruginosa (Pa) infection, but it remains unknown whether alterations at the tumor cell level can contribute to infection. This study explored how cellular changes associated with tumor metastasis influence Pa infection using highly metastatic MTLn3 cells and non-metastatic MTC cells as cell culture models. MTLn3 cells were found to be more sensitive to Pa infection than MTC cells based on increased translocation of the type III secretion effector, ExoS, into MTLn3 cells. Subsequent studies found that higher levels of ExoS translocation into MTLn3 cells related to Pa entry and secretion of ExoS within MTLn3 cells, rather than conventional ExoS translocation by external Pa. ExoS includes both Rho GTPase activating protein (GAP) and ADP-ribosyltransferase (ADPRT) enzyme activities, and differences in MTLn3 and MTC cell responsiveness to ExoS were found to relate to the targeting of ExoS-GAP activity to Rho GTPases. MTLn3 cell migration is mediated by RhoA activation at the leading edge, and inhibition of RhoA activity decreased ExoS translocation into MTLn3 cells to levels similar to those of MTC cells. The ability of Pa to be internalized and transfer ExoS more efficiently in association with Rho activation during tumor metastasis confirms that alterations in cell migration that occur in conjunction with tumor metastasis contribute to Pa infection in cancer patients. This study also raises the possibility that Pa might serve as a biological tool for dissecting or detecting cellular alterations associated with tumor metastasis.http://bio.biologists.org/content/2/9/891Tumor metastasisMTC and MTLn3 cellsPseudomonas aeruginosaRho GTPaseCell migration |
| spellingShingle | Matthew J. Novotny Dacie R. Bridge Karen H. Martin Scott A. Weed Robert B. Wysolmerski Joan C. Olson Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa Biology Open Tumor metastasis MTC and MTLn3 cells Pseudomonas aeruginosa Rho GTPase Cell migration |
| title | Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa |
| title_full | Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa |
| title_fullStr | Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa |
| title_full_unstemmed | Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa |
| title_short | Metastatic MTLn3 and non-metastatic MTC adenocarcinoma cells can be differentiated by Pseudomonas aeruginosa |
| title_sort | metastatic mtln3 and non metastatic mtc adenocarcinoma cells can be differentiated by pseudomonas aeruginosa |
| topic | Tumor metastasis MTC and MTLn3 cells Pseudomonas aeruginosa Rho GTPase Cell migration |
| url | http://bio.biologists.org/content/2/9/891 |
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