Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice
<p>Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types. We have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | , , , , |
| منشور في: |
2015
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513505659453440 |
|---|---|
| author | Julie Decock (44558) |
| author2 | Wouter Hendrickx (44559) Sally Thirkettle (702179) Ana Gutiérrez-Fernández (72539) Stephen D Robinson (16210301) Dylan R Edwards (19651870) |
| author2_role | author author author author author |
| author_facet | Julie Decock (44558) Wouter Hendrickx (44559) Sally Thirkettle (702179) Ana Gutiérrez-Fernández (72539) Stephen D Robinson (16210301) Dylan R Edwards (19651870) |
| author_role | author |
| dc.creator.none.fl_str_mv | Julie Decock (44558) Wouter Hendrickx (44559) Sally Thirkettle (702179) Ana Gutiérrez-Fernández (72539) Stephen D Robinson (16210301) Dylan R Edwards (19651870) |
| dc.date.none.fl_str_mv | 2015-03-14T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s13058-015-0545-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Pleiotropic_functions_of_the_tumor-_and_metastasis-suppressing_matrix_metalloproteinase-8_in_mammary_cancer_in_MMTV-PyMT_transgenic_mice/27001930 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Oncology and carcinogenesis Skin Papilloma PyMT Mouse Skin Squamous Cell Carcinoma TIMP Family Mmp8 Genotype |
| dc.title.none.fl_str_mv | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types. We have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to explore the effects of loss of MMP-8 on the incidence and progression of mammary carcinomas. In this aggressive mouse model of breast cancer, loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT; Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the 14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a lower vascularity than their heterozygote and null counterparts. No differences in macrophage infiltration were apparent throughout primary tumor development, though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild-type tumors. Using quantitative real-time RT-PCR, we tracked the expression of the entire Mmp and Timp gene families, observing a significant decrease in Mmp3 expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout the time course of the model, which was confirmed at the protein level. These findings provide novel insight into the suppressive action of MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP-8 likely has pleiotropic effects on innate immunity and angiogenesis that are reflected in changes in the protease web.</p><h2>Other Information</h2> <p> Published in: Breast Cancer Research<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13058-015-0545-8" target="_blank">https://dx.doi.org/10.1186/s13058-015-0545-8</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e8931cfdb613ba28d2eb56f004445927 |
| identifier_str_mv | 10.1186/s13058-015-0545-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27001930 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic miceJulie Decock (44558)Wouter Hendrickx (44559)Sally Thirkettle (702179)Ana Gutiérrez-Fernández (72539)Stephen D Robinson (16210301)Dylan R Edwards (19651870)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesImmunologyOncology and carcinogenesisSkin PapillomaPyMT MouseSkin Squamous Cell CarcinomaTIMP FamilyMmp8 Genotype<p>Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types. We have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to explore the effects of loss of MMP-8 on the incidence and progression of mammary carcinomas. In this aggressive mouse model of breast cancer, loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT; Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the 14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a lower vascularity than their heterozygote and null counterparts. No differences in macrophage infiltration were apparent throughout primary tumor development, though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild-type tumors. Using quantitative real-time RT-PCR, we tracked the expression of the entire Mmp and Timp gene families, observing a significant decrease in Mmp3 expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout the time course of the model, which was confirmed at the protein level. These findings provide novel insight into the suppressive action of MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP-8 likely has pleiotropic effects on innate immunity and angiogenesis that are reflected in changes in the protease web.</p><h2>Other Information</h2> <p> Published in: Breast Cancer Research<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13058-015-0545-8" target="_blank">https://dx.doi.org/10.1186/s13058-015-0545-8</a></p>2015-03-14T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13058-015-0545-8https://figshare.com/articles/journal_contribution/Pleiotropic_functions_of_the_tumor-_and_metastasis-suppressing_matrix_metalloproteinase-8_in_mammary_cancer_in_MMTV-PyMT_transgenic_mice/27001930CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270019302015-03-14T03:00:00Z |
| spellingShingle | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice Julie Decock (44558) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Oncology and carcinogenesis Skin Papilloma PyMT Mouse Skin Squamous Cell Carcinoma TIMP Family Mmp8 Genotype |
| status_str | publishedVersion |
| title | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| title_full | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| title_fullStr | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| title_full_unstemmed | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| title_short | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| title_sort | Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Immunology Oncology and carcinogenesis Skin Papilloma PyMT Mouse Skin Squamous Cell Carcinoma TIMP Family Mmp8 Genotype |