Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression
Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to...
Gespeichert in:
| Veröffentlicht in: | PloS one 2014-05, Vol.9 (5), p.e98624-e98624 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e98624 |
|---|---|
| container_issue | 5 |
| container_start_page | e98624 |
| container_title | PloS one |
| container_volume | 9 |
| creator | Bailey-Downs, Lora C Thorpe, Jessica E Disch, Bryan C Bastian, Anja Hauser, Paul J Farasyn, Taleah Berry, William L Hurst, Robert E Ihnat, Michael A |
| description | Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases) two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly) was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis. |
| doi_str_mv | 10.1371/journal.pone.0098624 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1530610907</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A417148613</galeid><doaj_id>oai_doaj_org_article_967fbcee865c4483aaa8b78b6ac2df83</doaj_id><sourcerecordid>A417148613</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-fd4948e33a82336768adc684f7d104ef58b594a03f467afe6fe2e1795677118a3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLgujFjEmTJumNsKxfAwsLft2G0_Sk0yVtxqRdVPzxZnZml6nshfSi4c1z3pycnJNlTylZUibpm0s_hQHccuMHXBJSKVHwe9kxrVixEAVh9w_WR9mjGC8JKZkS4mF2VHAl04ofZ3_e4RU6v-lxGHMYmtysIYAZMXS_Yez8kHubQ74JaFw3dAZc3vsG3VauA0IccwODwZC7aWjzvjPB9zgmPUWbfPR5D3NpE3wbMMbk_Th7YMFFfLL_n2TfPrz_evZpcX7xcXV2er4wslTjwja84goZA1UwJqRQ0BihuJUNJRxtqeqy4kCY5UKCRWGxQCqrUkhJqQJ2kj3f-W6cj3pfuKhpyYigpCIyEasd0Xi41JvQ9RB-aQ-dvhZ8aDWElL1DXQlpa4OoRGk4VwwAVC1VLcAUjVUseb3dnzbVPTYmVTaAm5nOd4ZurVt_pTlhVUlpMni1Nwj-x4Rx1H0XDToHA_rpOm9albIoVUJf_IPefbs91UK6QDdYn841W1N9yqmkXAm6zXt5B5W-BtOzpi6zXdJnAa9nAYkZ8efYwhSjXn35_P_sxfc5-_KAXSO4cR29m7btGOcg34Gpw2IMaG-LTIneDslNNfR2SPR-SFLYs8MHug26mQr2F0VNDuU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1530610907</pqid></control><display><type>article</type><title>Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Bailey-Downs, Lora C ; Thorpe, Jessica E ; Disch, Bryan C ; Bastian, Anja ; Hauser, Paul J ; Farasyn, Taleah ; Berry, William L ; Hurst, Robert E ; Ihnat, Michael A</creator><creatorcontrib>Bailey-Downs, Lora C ; Thorpe, Jessica E ; Disch, Bryan C ; Bastian, Anja ; Hauser, Paul J ; Farasyn, Taleah ; Berry, William L ; Hurst, Robert E ; Ihnat, Michael A</creatorcontrib><description>Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases) two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly) was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0098624</identifier><identifier>PMID: 24878664</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Animal models ; Animals ; Anthracyclines ; Biology and Life Sciences ; Brain ; Brain cancer ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer ; Cancer therapies ; Cell Line, Tumor ; Chemical properties ; Chemotherapy ; Disease Progression ; Dormancy ; Doxorubicin ; Doxorubicin - pharmacology ; Drug development ; Female ; Immunosuppressive agents ; Implantation ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Lung Neoplasms - secondary ; Mammary Neoplasms, Experimental - drug therapy ; Mammary Neoplasms, Experimental - pathology ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis - drug therapy ; Neoplasm Metastasis - pathology ; Neoplasm Micrometastasis - drug therapy ; Neoplasm Micrometastasis - pathology ; Pharmaceutical sciences ; Pharmacy ; Research and Analysis Methods ; Titration ; Tumorigenesis ; Tumors ; Urology</subject><ispartof>PloS one, 2014-05, Vol.9 (5), p.e98624-e98624</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Bailey-Downs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Bailey-Downs et al 2014 Bailey-Downs et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-fd4948e33a82336768adc684f7d104ef58b594a03f467afe6fe2e1795677118a3</citedby><cites>FETCH-LOGICAL-c758t-fd4948e33a82336768adc684f7d104ef58b594a03f467afe6fe2e1795677118a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039511/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039511/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24878664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bailey-Downs, Lora C</creatorcontrib><creatorcontrib>Thorpe, Jessica E</creatorcontrib><creatorcontrib>Disch, Bryan C</creatorcontrib><creatorcontrib>Bastian, Anja</creatorcontrib><creatorcontrib>Hauser, Paul J</creatorcontrib><creatorcontrib>Farasyn, Taleah</creatorcontrib><creatorcontrib>Berry, William L</creatorcontrib><creatorcontrib>Hurst, Robert E</creatorcontrib><creatorcontrib>Ihnat, Michael A</creatorcontrib><title>Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases) two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly) was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis.</description><subject>Activation</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anthracyclines</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemical properties</subject><subject>Chemotherapy</subject><subject>Disease Progression</subject><subject>Dormancy</subject><subject>Doxorubicin</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug development</subject><subject>Female</subject><subject>Immunosuppressive agents</subject><subject>Implantation</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - secondary</subject><subject>Mammary Neoplasms, Experimental - drug therapy</subject><subject>Mammary Neoplasms, Experimental - pathology</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Metastasis - drug therapy</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Neoplasm Micrometastasis - drug therapy</subject><subject>Neoplasm Micrometastasis - pathology</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Research and Analysis Methods</subject><subject>Titration</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Urology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjEmTJumNsKxfAwsLft2G0_Sk0yVtxqRdVPzxZnZml6nshfSi4c1z3pycnJNlTylZUibpm0s_hQHccuMHXBJSKVHwe9kxrVixEAVh9w_WR9mjGC8JKZkS4mF2VHAl04ofZ3_e4RU6v-lxGHMYmtysIYAZMXS_Yez8kHubQ74JaFw3dAZc3vsG3VauA0IccwODwZC7aWjzvjPB9zgmPUWbfPR5D3NpE3wbMMbk_Th7YMFFfLL_n2TfPrz_evZpcX7xcXV2er4wslTjwja84goZA1UwJqRQ0BihuJUNJRxtqeqy4kCY5UKCRWGxQCqrUkhJqQJ2kj3f-W6cj3pfuKhpyYigpCIyEasd0Xi41JvQ9RB-aQ-dvhZ8aDWElL1DXQlpa4OoRGk4VwwAVC1VLcAUjVUseb3dnzbVPTYmVTaAm5nOd4ZurVt_pTlhVUlpMni1Nwj-x4Rx1H0XDToHA_rpOm9albIoVUJf_IPefbs91UK6QDdYn841W1N9yqmkXAm6zXt5B5W-BtOzpi6zXdJnAa9nAYkZ8efYwhSjXn35_P_sxfc5-_KAXSO4cR29m7btGOcg34Gpw2IMaG-LTIneDslNNfR2SPR-SFLYs8MHug26mQr2F0VNDuU</recordid><startdate>20140530</startdate><enddate>20140530</enddate><creator>Bailey-Downs, Lora C</creator><creator>Thorpe, Jessica E</creator><creator>Disch, Bryan C</creator><creator>Bastian, Anja</creator><creator>Hauser, Paul J</creator><creator>Farasyn, Taleah</creator><creator>Berry, William L</creator><creator>Hurst, Robert E</creator><creator>Ihnat, Michael A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140530</creationdate><title>Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression</title><author>Bailey-Downs, Lora C ; Thorpe, Jessica E ; Disch, Bryan C ; Bastian, Anja ; Hauser, Paul J ; Farasyn, Taleah ; Berry, William L ; Hurst, Robert E ; Ihnat, Michael A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-fd4948e33a82336768adc684f7d104ef58b594a03f467afe6fe2e1795677118a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activation</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anthracyclines</topic><topic>Biology and Life Sciences</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Chemical properties</topic><topic>Chemotherapy</topic><topic>Disease Progression</topic><topic>Dormancy</topic><topic>Doxorubicin</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug development</topic><topic>Female</topic><topic>Immunosuppressive agents</topic><topic>Implantation</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - secondary</topic><topic>Mammary Neoplasms, Experimental - drug therapy</topic><topic>Mammary Neoplasms, Experimental - pathology</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasm Metastasis - drug therapy</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Neoplasm Micrometastasis - drug therapy</topic><topic>Neoplasm Micrometastasis - pathology</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacy</topic><topic>Research and Analysis Methods</topic><topic>Titration</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bailey-Downs, Lora C</creatorcontrib><creatorcontrib>Thorpe, Jessica E</creatorcontrib><creatorcontrib>Disch, Bryan C</creatorcontrib><creatorcontrib>Bastian, Anja</creatorcontrib><creatorcontrib>Hauser, Paul J</creatorcontrib><creatorcontrib>Farasyn, Taleah</creatorcontrib><creatorcontrib>Berry, William L</creatorcontrib><creatorcontrib>Hurst, Robert E</creatorcontrib><creatorcontrib>Ihnat, Michael A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bailey-Downs, Lora C</au><au>Thorpe, Jessica E</au><au>Disch, Bryan C</au><au>Bastian, Anja</au><au>Hauser, Paul J</au><au>Farasyn, Taleah</au><au>Berry, William L</au><au>Hurst, Robert E</au><au>Ihnat, Michael A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-05-30</date><risdate>2014</risdate><volume>9</volume><issue>5</issue><spage>e98624</spage><epage>e98624</epage><pages>e98624-e98624</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases) two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly) was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24878664</pmid><doi>10.1371/journal.pone.0098624</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-05, Vol.9 (5), p.e98624-e98624 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1530610907 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Activation Animal models Animals Anthracyclines Biology and Life Sciences Brain Brain cancer Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer Cancer therapies Cell Line, Tumor Chemical properties Chemotherapy Disease Progression Dormancy Doxorubicin Doxorubicin - pharmacology Drug development Female Immunosuppressive agents Implantation Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - pathology Lung Neoplasms - secondary Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - pathology Medicine Medicine and Health Sciences Metastases Metastasis Mice Mice, Inbred BALB C Neoplasm Metastasis - drug therapy Neoplasm Metastasis - pathology Neoplasm Micrometastasis - drug therapy Neoplasm Micrometastasis - pathology Pharmaceutical sciences Pharmacy Research and Analysis Methods Titration Tumorigenesis Tumors Urology |
| title | Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T14%3A49%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20and%20characterization%20of%20a%20preclinical%20model%20of%20breast%20cancer%20lung%20micrometastatic%20to%20macrometastatic%20progression&rft.jtitle=PloS%20one&rft.au=Bailey-Downs,%20Lora%20C&rft.date=2014-05-30&rft.volume=9&rft.issue=5&rft.spage=e98624&rft.epage=e98624&rft.pages=e98624-e98624&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0098624&rft_dat=%3Cgale_plos_%3EA417148613%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1530610907&rft_id=info:pmid/24878664&rft_galeid=A417148613&rft_doaj_id=oai_doaj_org_article_967fbcee865c4483aaa8b78b6ac2df83&rfr_iscdi=true |