Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice
Breast cancer metastasizes to bone in the majority of patients with advanced disease. We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were...
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description | Breast cancer metastasizes to bone in the majority of patients with advanced disease. We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n = 7-10 mice/group). Control mice (n = 6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice. |
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We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n = 7-10 mice/group). Control mice (n = 6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0180886</identifier><identifier>PMID: 28750038</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biocompatibility ; Biology ; Biology and Life Sciences ; Bioluminescence ; Biomedical materials ; Bone (cortical) ; Bone cancer ; Bone growth ; Bone Remodeling - drug effects ; Bone turnover ; Breast cancer ; Calcium ; Calcium (dietary) ; Calcium (Nutrient) ; Calcium, Dietary - pharmacology ; Cancellous Bone - diagnostic imaging ; Cancellous Bone - drug effects ; Cancellous Bone - pathology ; Cancer metastasis ; Carcinoma ; Cell Line, Tumor ; Computed tomography ; Cortical bone ; Development and progression ; Diet ; Disease Progression ; Female ; Food science ; Gordon, Kenneth ; Health care ; Histology ; Infiltration ; Inoculation ; Kinases ; Laboratory animals ; Lung cancer ; Lungs ; Mammary gland ; Mammary Neoplasms, Animal - pathology ; Medicine and Health Sciences ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Muscles ; Neoplasm Metastasis ; Nutrient deficiency ; Nutrition research ; Osteogenesis ; Osteolysis ; Physiological aspects ; Public health ; Quality of life ; Research and Analysis Methods ; Tibia ; Tibia - diagnostic imaging ; Tibia - drug effects ; Tibia - pathology ; Tumor Burden - drug effects ; Tumor cells ; Tumors ; Veterinary colleges ; Veterinary medicine ; X-Ray Microtomography</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0180886-e0180886</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Wang 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>2017 Wang et al 2017 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-745a77c83c6f689b3a7e60ab6195c96caefe3540b2718e6c414b24f655e07e1a3</citedby><cites>FETCH-LOGICAL-c692t-745a77c83c6f689b3a7e60ab6195c96caefe3540b2718e6c414b24f655e07e1a3</cites><orcidid>0000-0003-2697-7066</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531562/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531562/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28750038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Heymann, Dominique</contributor><creatorcontrib>Wang, Wendan</creatorcontrib><creatorcontrib>Gordon, Jody L</creatorcontrib><creatorcontrib>Philbrick, Kenneth A</creatorcontrib><creatorcontrib>Yang, Xujuan</creatorcontrib><creatorcontrib>Branscum, Adam J</creatorcontrib><creatorcontrib>Löhr, Christiane V</creatorcontrib><creatorcontrib>Haschek, Wanda M</creatorcontrib><creatorcontrib>Turner, Russell T</creatorcontrib><creatorcontrib>Iwaniec, Urszula T</creatorcontrib><creatorcontrib>Helferich, William G</creatorcontrib><title>Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Breast cancer metastasizes to bone in the majority of patients with advanced disease. We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n = 7-10 mice/group). Control mice (n = 6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice.</description><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Bioluminescence</subject><subject>Biomedical materials</subject><subject>Bone (cortical)</subject><subject>Bone cancer</subject><subject>Bone growth</subject><subject>Bone Remodeling - drug effects</subject><subject>Bone turnover</subject><subject>Breast cancer</subject><subject>Calcium</subject><subject>Calcium (dietary)</subject><subject>Calcium (Nutrient)</subject><subject>Calcium, Dietary - pharmacology</subject><subject>Cancellous Bone - diagnostic imaging</subject><subject>Cancellous Bone - drug effects</subject><subject>Cancellous Bone - pathology</subject><subject>Cancer metastasis</subject><subject>Carcinoma</subject><subject>Cell Line, Tumor</subject><subject>Computed tomography</subject><subject>Cortical bone</subject><subject>Development and progression</subject><subject>Diet</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Food science</subject><subject>Gordon, Kenneth</subject><subject>Health care</subject><subject>Histology</subject><subject>Infiltration</subject><subject>Inoculation</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Lung cancer</subject><subject>Lungs</subject><subject>Mammary gland</subject><subject>Mammary Neoplasms, Animal - pathology</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Muscles</subject><subject>Neoplasm Metastasis</subject><subject>Nutrient deficiency</subject><subject>Nutrition research</subject><subject>Osteogenesis</subject><subject>Osteolysis</subject><subject>Physiological aspects</subject><subject>Public health</subject><subject>Quality of life</subject><subject>Research and Analysis Methods</subject><subject>Tibia</subject><subject>Tibia - diagnostic imaging</subject><subject>Tibia - drug effects</subject><subject>Tibia - pathology</subject><subject>Tumor Burden - drug effects</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><subject>X-Ray Microtomography</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDgujFjEnz2RthWfwYGFjQ1TsJaXo6k6FtZpNW3X9v6nSXqeyF5CIhec6bnPfkZNlzgpeESvJu54fQmWa59x0sMVFYKfEgOyUFzRcix_Th0fokexLjDmNOlRCPs5NcSY4xVafZj7X_haxprBtaVDnoketsABMhInZFUGva1oQb1A-tDwkM1nW-NchC06ByCBV0yHQVKtMr0N70W9_4zU0SQa2z8DR7VJsmwrNpPsu-ffxwdfF5sb78tLo4Xy-sKPJ-IRk3UlpFraiFKkpqJAhsSkEKbgthDdRAOcNlLokCYRlhZc5qwTlgCcTQs-zlQXff-KgnZ6LOMZE8L5IBiVgdiMqbnd4HN2alvXH674YPG21C72wDWknMZQm0LkTJcqZULQErKmtKLbbAktb76bahbKGy0PXBNDPR-Unntnrjf2rOKeEiTwJvJoHgrweIvW5dHB01HfghalLkTGAmcpnQV_-g92c3URuTEnBd7dO9dhTV56woRjFZJGp5D5VGBalYqYC1S_uzgLezgMT08LvfmCFGvfr65f_Zy-9z9vURuwXT9Nvom6F3votzkB1AG3yMAeo7kwnWYxfcuqHHLtBTF6SwF8cFugu6_fb0D4fqANM</recordid><startdate>20170727</startdate><enddate>20170727</enddate><creator>Wang, Wendan</creator><creator>Gordon, Jody L</creator><creator>Philbrick, Kenneth A</creator><creator>Yang, Xujuan</creator><creator>Branscum, Adam J</creator><creator>Löhr, Christiane V</creator><creator>Haschek, Wanda M</creator><creator>Turner, Russell T</creator><creator>Iwaniec, Urszula T</creator><creator>Helferich, William G</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>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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2697-7066</orcidid></search><sort><creationdate>20170727</creationdate><title>Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice</title><author>Wang, Wendan ; Gordon, Jody L ; Philbrick, Kenneth A ; Yang, Xujuan ; Branscum, Adam J ; Löhr, Christiane V ; Haschek, Wanda M ; Turner, Russell T ; Iwaniec, Urszula T ; Helferich, William G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-745a77c83c6f689b3a7e60ab6195c96caefe3540b2718e6c414b24f655e07e1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Bioluminescence</topic><topic>Biomedical materials</topic><topic>Bone (cortical)</topic><topic>Bone cancer</topic><topic>Bone growth</topic><topic>Bone Remodeling - drug effects</topic><topic>Bone turnover</topic><topic>Breast cancer</topic><topic>Calcium</topic><topic>Calcium (dietary)</topic><topic>Calcium (Nutrient)</topic><topic>Calcium, Dietary - pharmacology</topic><topic>Cancellous Bone - diagnostic imaging</topic><topic>Cancellous Bone - drug effects</topic><topic>Cancellous Bone - pathology</topic><topic>Cancer metastasis</topic><topic>Carcinoma</topic><topic>Cell Line, Tumor</topic><topic>Computed tomography</topic><topic>Cortical bone</topic><topic>Development and progression</topic><topic>Diet</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Food science</topic><topic>Gordon, Kenneth</topic><topic>Health care</topic><topic>Histology</topic><topic>Infiltration</topic><topic>Inoculation</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Lung cancer</topic><topic>Lungs</topic><topic>Mammary gland</topic><topic>Mammary Neoplasms, Animal - pathology</topic><topic>Medicine and Health Sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Muscles</topic><topic>Neoplasm Metastasis</topic><topic>Nutrient deficiency</topic><topic>Nutrition research</topic><topic>Osteogenesis</topic><topic>Osteolysis</topic><topic>Physiological aspects</topic><topic>Public health</topic><topic>Quality of life</topic><topic>Research and Analysis Methods</topic><topic>Tibia</topic><topic>Tibia - diagnostic imaging</topic><topic>Tibia - drug effects</topic><topic>Tibia - pathology</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Veterinary colleges</topic><topic>Veterinary medicine</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Wendan</creatorcontrib><creatorcontrib>Gordon, Jody L</creatorcontrib><creatorcontrib>Philbrick, Kenneth A</creatorcontrib><creatorcontrib>Yang, Xujuan</creatorcontrib><creatorcontrib>Branscum, Adam J</creatorcontrib><creatorcontrib>Löhr, Christiane V</creatorcontrib><creatorcontrib>Haschek, Wanda M</creatorcontrib><creatorcontrib>Turner, Russell T</creatorcontrib><creatorcontrib>Iwaniec, Urszula T</creatorcontrib><creatorcontrib>Helferich, William G</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 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 - 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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>Wang, Wendan</au><au>Gordon, Jody L</au><au>Philbrick, Kenneth A</au><au>Yang, Xujuan</au><au>Branscum, Adam J</au><au>Löhr, Christiane V</au><au>Haschek, Wanda M</au><au>Turner, Russell T</au><au>Iwaniec, Urszula T</au><au>Helferich, William G</au><au>Heymann, Dominique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-07-27</date><risdate>2017</risdate><volume>12</volume><issue>7</issue><spage>e0180886</spage><epage>e0180886</epage><pages>e0180886-e0180886</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Breast cancer metastasizes to bone in the majority of patients with advanced disease. We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n = 7-10 mice/group). Control mice (n = 6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28750038</pmid><doi>10.1371/journal.pone.0180886</doi><tpages>e0180886</tpages><orcidid>https://orcid.org/0000-0003-2697-7066</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2017-07, Vol.12 (7), p.e0180886-e0180886 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2017529203 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Animals Biocompatibility Biology Biology and Life Sciences Bioluminescence Biomedical materials Bone (cortical) Bone cancer Bone growth Bone Remodeling - drug effects Bone turnover Breast cancer Calcium Calcium (dietary) Calcium (Nutrient) Calcium, Dietary - pharmacology Cancellous Bone - diagnostic imaging Cancellous Bone - drug effects Cancellous Bone - pathology Cancer metastasis Carcinoma Cell Line, Tumor Computed tomography Cortical bone Development and progression Diet Disease Progression Female Food science Gordon, Kenneth Health care Histology Infiltration Inoculation Kinases Laboratory animals Lung cancer Lungs Mammary gland Mammary Neoplasms, Animal - pathology Medicine and Health Sciences Metastases Metastasis Mice Mice, Inbred BALB C Muscles Neoplasm Metastasis Nutrient deficiency Nutrition research Osteogenesis Osteolysis Physiological aspects Public health Quality of life Research and Analysis Methods Tibia Tibia - diagnostic imaging Tibia - drug effects Tibia - pathology Tumor Burden - drug effects Tumor cells Tumors Veterinary colleges Veterinary medicine X-Ray Microtomography |
title | Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice |
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