No effect of NGAL/lipocalin-2 on aggressiveness of cancer in the MMTV-PyMT/FVB/N mouse model for breast cancer
NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models...
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| Veröffentlicht in: | PloS one 2012-06, Vol.7 (6), p.e39646-e39646 |
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| creator | Cramer, Elisabeth P Glenthøj, Andreas Häger, Mattias Juncker-Jensen, Anna Engelholm, Lars H Santoni-Rugiu, Eric Lund, Leif R Laerum, Ole D Cowland, Jack B Borregaard, Niels |
| description | NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed into the same FVB/N background. All mice developed tumors by week 8. The mice were sacrificed on week 13 and tissue was processed for biochemical and histological analysis. The total tumor volume and number of metastases were quantitated in 26 lipocalin-2-deficient mice and 34 wild-type controls. Lipocalin-2 expression in tumors of MMTV-PyMT-positive and wild-type mice was assessed by quantitative real-time PCR and by immunohistochemistry. The expression of the lipocalin-2 receptors 24p3R and megalin and of Mmp-9, transferrin receptor, and Bdh2 (a producer of a mammalian siderophore) were quantitated by real-time PCR. No significant difference was observed between wild-type and lipocalin-2-deficient mice. Lipocalin-2 was highly expressed in tumors from wild-type mice, but the expression did not correlate with tumor size. No effect of lipocalin-2 was observed with respect to time to tumor appearance, total tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus questioning the role of lipocalin-2 in cancer development. |
| doi_str_mv | 10.1371/journal.pone.0039646 |
| format | Article |
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It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed into the same FVB/N background. All mice developed tumors by week 8. The mice were sacrificed on week 13 and tissue was processed for biochemical and histological analysis. The total tumor volume and number of metastases were quantitated in 26 lipocalin-2-deficient mice and 34 wild-type controls. Lipocalin-2 expression in tumors of MMTV-PyMT-positive and wild-type mice was assessed by quantitative real-time PCR and by immunohistochemistry. The expression of the lipocalin-2 receptors 24p3R and megalin and of Mmp-9, transferrin receptor, and Bdh2 (a producer of a mammalian siderophore) were quantitated by real-time PCR. No significant difference was observed between wild-type and lipocalin-2-deficient mice. Lipocalin-2 was highly expressed in tumors from wild-type mice, but the expression did not correlate with tumor size. No effect of lipocalin-2 was observed with respect to time to tumor appearance, total tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus questioning the role of lipocalin-2 in cancer development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0039646</identifier><identifier>PMID: 22737251</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute-Phase Proteins - metabolism ; Analysis ; Animal models ; Animals ; Antigens, Polyomavirus Transforming - metabolism ; Apoptosis ; Biology ; Breast cancer ; Cancer ; Cell Line, Tumor ; Disease Models, Animal ; Experiments ; Female ; Gelatinase B ; Gene Expression Regulation, Neoplastic ; Granulocytes ; Granulocytes - cytology ; Hematology ; Histology ; Humans ; Immunohistochemistry ; Immunohistochemistry - methods ; Laboratories ; Lipocalin ; Lipocalin-2 ; Lipocalins - metabolism ; Low Density Lipoprotein Receptor-Related Protein-2 - biosynthesis ; Male ; Matrix Metalloproteinase 9 - biosynthesis ; Medicine ; Metastases ; Metastasis ; Mice ; Mice, Knockout ; Neutrophils ; Nitric oxide ; Oncogene Proteins - metabolism ; Protein binding ; Proteins ; Real time ; Receptors ; Receptors, Cell Surface - biosynthesis ; Receptors, Transferrin - biosynthesis ; Rodents ; Studies ; Transferrin ; Transferrins ; Tumor antigens ; Tumors ; Urine ; Viruses</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e39646-e39646</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Cramer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Cramer et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-771d1f129dba0535891e35bb0e04a3f4a24e77ee0ba17e39eb3eb30d525c0b923</citedby><cites>FETCH-LOGICAL-c692t-771d1f129dba0535891e35bb0e04a3f4a24e77ee0ba17e39eb3eb30d525c0b923</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/PMC3380857/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380857/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22737251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cramer, Elisabeth P</creatorcontrib><creatorcontrib>Glenthøj, Andreas</creatorcontrib><creatorcontrib>Häger, Mattias</creatorcontrib><creatorcontrib>Juncker-Jensen, Anna</creatorcontrib><creatorcontrib>Engelholm, Lars H</creatorcontrib><creatorcontrib>Santoni-Rugiu, Eric</creatorcontrib><creatorcontrib>Lund, Leif R</creatorcontrib><creatorcontrib>Laerum, Ole D</creatorcontrib><creatorcontrib>Cowland, Jack B</creatorcontrib><creatorcontrib>Borregaard, Niels</creatorcontrib><title>No effect of NGAL/lipocalin-2 on aggressiveness of cancer in the MMTV-PyMT/FVB/N mouse model for breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed into the same FVB/N background. All mice developed tumors by week 8. The mice were sacrificed on week 13 and tissue was processed for biochemical and histological analysis. The total tumor volume and number of metastases were quantitated in 26 lipocalin-2-deficient mice and 34 wild-type controls. Lipocalin-2 expression in tumors of MMTV-PyMT-positive and wild-type mice was assessed by quantitative real-time PCR and by immunohistochemistry. 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We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus questioning the role of lipocalin-2 in cancer development.</description><subject>Acute-Phase Proteins - metabolism</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens, Polyomavirus Transforming - metabolism</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Disease Models, Animal</subject><subject>Experiments</subject><subject>Female</subject><subject>Gelatinase B</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Granulocytes</subject><subject>Granulocytes - cytology</subject><subject>Hematology</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunohistochemistry - methods</subject><subject>Laboratories</subject><subject>Lipocalin</subject><subject>Lipocalin-2</subject><subject>Lipocalins - 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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>Cramer, Elisabeth P</au><au>Glenthøj, Andreas</au><au>Häger, Mattias</au><au>Juncker-Jensen, Anna</au><au>Engelholm, Lars H</au><au>Santoni-Rugiu, Eric</au><au>Lund, Leif R</au><au>Laerum, Ole D</au><au>Cowland, Jack B</au><au>Borregaard, Niels</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>No effect of NGAL/lipocalin-2 on aggressiveness of cancer in the MMTV-PyMT/FVB/N mouse model for breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-06-21</date><risdate>2012</risdate><volume>7</volume><issue>6</issue><spage>e39646</spage><epage>e39646</epage><pages>e39646-e39646</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed into the same FVB/N background. All mice developed tumors by week 8. The mice were sacrificed on week 13 and tissue was processed for biochemical and histological analysis. The total tumor volume and number of metastases were quantitated in 26 lipocalin-2-deficient mice and 34 wild-type controls. Lipocalin-2 expression in tumors of MMTV-PyMT-positive and wild-type mice was assessed by quantitative real-time PCR and by immunohistochemistry. The expression of the lipocalin-2 receptors 24p3R and megalin and of Mmp-9, transferrin receptor, and Bdh2 (a producer of a mammalian siderophore) were quantitated by real-time PCR. No significant difference was observed between wild-type and lipocalin-2-deficient mice. Lipocalin-2 was highly expressed in tumors from wild-type mice, but the expression did not correlate with tumor size. No effect of lipocalin-2 was observed with respect to time to tumor appearance, total tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus questioning the role of lipocalin-2 in cancer development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22737251</pmid><doi>10.1371/journal.pone.0039646</doi><tpages>e39646</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-06, Vol.7 (6), p.e39646-e39646 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1325027221 |
| 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 | Acute-Phase Proteins - metabolism Analysis Animal models Animals Antigens, Polyomavirus Transforming - metabolism Apoptosis Biology Breast cancer Cancer Cell Line, Tumor Disease Models, Animal Experiments Female Gelatinase B Gene Expression Regulation, Neoplastic Granulocytes Granulocytes - cytology Hematology Histology Humans Immunohistochemistry Immunohistochemistry - methods Laboratories Lipocalin Lipocalin-2 Lipocalins - metabolism Low Density Lipoprotein Receptor-Related Protein-2 - biosynthesis Male Matrix Metalloproteinase 9 - biosynthesis Medicine Metastases Metastasis Mice Mice, Knockout Neutrophils Nitric oxide Oncogene Proteins - metabolism Protein binding Proteins Real time Receptors Receptors, Cell Surface - biosynthesis Receptors, Transferrin - biosynthesis Rodents Studies Transferrin Transferrins Tumor antigens Tumors Urine Viruses |
| title | No effect of NGAL/lipocalin-2 on aggressiveness of cancer in the MMTV-PyMT/FVB/N mouse model for breast cancer |
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