Nicotine Promotes Tumor Growth and Metastasis in Mouse Models of Lung Cancer
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{"title"=>"Nicotine promotes tumor growth and metastasis in mouse models of lung cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Rebecca", "last_name"=>"Davis", "scopus_author_id"=>"55482697400"}, {"first_name"=>"Wasia", "last_name"=>"Rizwani", "scopus_author_id"=>"25951803500"}, {"first_name"=>"Sarmistha", "last_name"=>"Banerjee", "scopus_author_id"=>"10639110900"}, {"first_name"=>"Michelle", "last_name"=>"Kovacs", "scopus_author_id"=>"25951531400"}, {"first_name"=>"Eric", "last_name"=>"Haura", "scopus_author_id"=>"6603533598"}, {"first_name"=>"Domenico", "last_name"=>"Coppola", "scopus_author_id"=>"7005933277"}, {"first_name"=>"Srikumar", "last_name"=>"Chellappan", "scopus_author_id"=>"7003601778"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-70449433017", "sgr"=>"70449433017", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0007524", "pmid"=>"19841737", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"355609635"}, "id"=>"b5bdb516-c638-3ed7-8fb8-dfda24eb1b57", "abstract"=>"BACKGROUND: Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.\\n\\nMETHODS AND FINDINGS: In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7) nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.\\n\\nCONCLUSIONS: Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens.", "link"=>"http://www.mendeley.com/research/nicotine-promotes-tumor-growth-metastasis-mouse-models-lung-cancer", "reader_count"=>41, "reader_count_by_academic_status"=>{"Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>6, "Student > Bachelor"=>6, "Professor"=>6}, "reader_count_by_user_role"=>{"Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>6, "Student > Bachelor"=>6, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>14, "Agricultural and Biological Sciences"=>10, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Psychology"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"United States"=>3, "Brazil"=>1, "Switzerland"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/879034"], "description"=>"<p>(A) E-Cadherin staining of A/J lung tumors induced by NNK or NNK+nicotine. (B) Quantitation of E-Cadherin intensity in tumors (C) β-Catenin staining of A/J lung tumors induced by NNK or NNK+nicotine. (D) Quantitation of membranous β-Catenin. (E) ZO-1 staining of A/J lung tumors induced by NNK or NNK+nicotine. (F) Quantitation of membranous ZO-1.</p>", "links"=>[], "tags"=>["reduced", "epithelial", "markers"], "article_id"=>549479, "categories"=>["Molecular Biology", "Cancer", "Cell Biology"], "users"=>["Rebecca Davis", "Wasia Rizwani", "Sarmistha Banerjee", "Michelle Kovacs", "Eric Haura", "Domenico Coppola", "Srikumar Chellappan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007524.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nicotine_reduced_the_expression_of_epithelial_markers_in_A_J_mice_/549479", "title"=>"Nicotine reduced the expression of epithelial markers in A/J mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:09:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/878779"], "description"=>"<p>(A) H&E staining of transverse sectioning of lungs (B) Representative scanned images of H&E stained coronal lung sections, tumors are outlined by boxes. Images were scanned at 20×magnification. (C) Nicotine increases the average number of lung tumors per mouse, <i>p</i> = 0.01, <i>n</i> = 8. (D) Nicotine increased tumor size significantly in A/J mice.</p>", "links"=>[], "tags"=>["increases", "nnk", "induced"], "article_id"=>549227, "categories"=>["Molecular Biology", "Cancer", "Cell Biology"], "users"=>["Rebecca Davis", "Wasia Rizwani", "Sarmistha Banerjee", "Michelle Kovacs", "Eric Haura", "Domenico Coppola", "Srikumar Chellappan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007524.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nicotine_increases_number_and_size_of_NNK_induced_lung_tumors_/549227", "title"=>"Nicotine increases number and size of NNK induced lung tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:07:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/878600"], "description"=>"<p>(A) Nicotine treated mice (1 mg/kg) displayed higher incidence of tumor recurrence following surgical removal of tumors compared to the vehicle control group, <i>p</i> = 0.01, <i>n</i> = 16. (B) Nicotine treated mice display significantly more lung metastasis from primary Line1 s.c. tumors. (C) H&E staining of lungs from vehicle and nicotine treated mice, nicotine treated mice display larger tumors as indicated by arrows. (D) Graph displaying the average total number of lung tumors per mouse in vehicle and nicotine (1 mg/kg) treated mice, p = 0.001, <i>n</i> = 16. (E) Graph displaying the average total number of lung tumors per mouse in control and nicotine patch (25 mg/kg) treated mice, p = 0.02, n = 16.</p>", "links"=>[], "tags"=>["increases", "metastatic"], "article_id"=>549044, "categories"=>["Molecular Biology", "Cancer", "Cell Biology"], "users"=>["Rebecca Davis", "Wasia Rizwani", "Sarmistha Banerjee", "Michelle Kovacs", "Eric Haura", "Domenico Coppola", "Srikumar Chellappan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007524.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nicotine_increases_metastatic_potential_/549044", "title"=>"Nicotine increases metastatic potential.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:06:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/878918"], "description"=>"<p>(A) Quiescent Line1 cells were treated with 1 µM nicotine for 18 h in the presence or absence of α-BT, an α<sub>7</sub> nAChR subunit inhibitor. Nicotine enhances α<sub>7</sub> expression, while α-BT reverses this. (B) Reverse-transcriptase coupled-PCR showing the expression of α<sub>7</sub> nAChR subunits in serum starved Line1 cells treated with nicotine for 24 h. PCR for actin was used as the loading control. (C) α<sub>7</sub> nAChR staining of A/J lung tumors induced by NNK or induced by NNK and exposed to Nicotine. Nicotine enhances the expression of this receptor subunit. (D) Quantitation of α<sub>7</sub> nAChR expression in vehicle and nicotine treated tumors.</p>", "links"=>[], "tags"=>["enhances", "nachr", "subunit", "line1"], "article_id"=>549361, "categories"=>["Molecular Biology", "Cancer", "Cell Biology"], "users"=>["Rebecca Davis", "Wasia Rizwani", "Sarmistha Banerjee", "Michelle Kovacs", "Eric Haura", "Domenico Coppola", "Srikumar Chellappan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007524.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nicotine_enhances_7_nAChR_subunit_expression_in_Line1_cells_/549361", "title"=>"Nicotine enhances α<sub>7</sub> nAChR subunit expression in Line1 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:08:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/878470"], "description"=>"<p>(A) Nicotine (1 µM) promotes S-phase entry of serum starved Line1 cells in BrdU incorporation assays. (B) Nicotine (1 mg/kg) significantly increases Line1 tumor growth in Balb/c mice when administered by i.p. injection thrice weekly, p = 0.002, n = 10. (C) Nicotine (25 mg/kg/daily) also significantly increases Line1 tumor growth when administered by transdermal patches p = 0.019, n = 14.</p>", "links"=>[], "tags"=>["line1"], "article_id"=>548919, "categories"=>["Molecular Biology", "Cancer", "Cell Biology"], "users"=>["Rebecca Davis", "Wasia Rizwani", "Sarmistha Banerjee", "Michelle Kovacs", "Eric Haura", "Domenico Coppola", "Srikumar Chellappan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007524.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nicotine_promotes_the_growth_of_Line1_cells_/548919", "title"=>"Nicotine promotes the growth of Line1 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:05:57"}

PMC Usage Stats | Further Information

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