{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T07:53:45Z","timestamp":1774079625283,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Recent studies suggest that angiopoietin-like protein 2 (ANGPTL2) is one of the factors contributing to disease progression in distant organs associated with periodontitis. We previously reported that periodontitis promotes hepatocellular carcinoma and that ANGPTL2 may be involved in tumor progression. Based on these findings, we herein investigated the role of periodontitis-induced ANGPTL2 in the progression of colorectal cancer (CRC) in mice. Methods: Male C57BL\/6 mice were divided into control and periodontitis groups. Colorectal tumors were induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Periodontitis was induced by silk ligation. In addition, the model was enhanced by repeated gingival administration of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis, a periodontal pathogen, to better mimic clinical conditions. Tumor development and ANGPTL2 expression in periodontal tissues, colorectal tumors, and serum were assessed by histology, immunostaining, and enzyme-linked immunosorbent assay. Results: Ligation and administration of P. gingivalis LPS resulted in significant alveolar bone resorption. The periodontitis group exhibited a significantly increased colorectal tumor burden compared with the control group. ANGPTL2 expression was markedly elevated in periodontal tissues, serum, and colorectal tumors in the periodontitis group. Histological analysis revealed increased tumor cell proliferation and enhanced inflammation in the periodontitis group relative to controls. These findings suggest a possible association between periodontitis-associated inflammation, elevated ANGPTL2 levels, and CRC progression in this experimental model. Conclusions: In this experimental model, experimental periodontitis was accompanied by concurrent increases in both local and systemic ANGPTL2 expression and accelerated growth of colorectal tumors. These findings suggest a potential association between periodontal inflammation, increased ANGPTL2 levels, and colorectal tumor progression.<\/jats:p>","DOI":"10.3390\/jcm15062359","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"2359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Production of Angiopoietin-like Protein 2 in a Ligature- and LPS-Induced Periodontitis Mouse Model May Promote Colorectal Tumor Progression"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1964-365X","authenticated-orcid":false,"given":"Mika","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genta","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1701-0381","authenticated-orcid":false,"given":"Kodai","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1853-2896","authenticated-orcid":false,"given":"Daiki","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9586-5458","authenticated-orcid":false,"given":"Nayu","family":"Tachikawa","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0466-0878","authenticated-orcid":false,"given":"Kota","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-5340","authenticated-orcid":false,"given":"Tasuku","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-0405","authenticated-orcid":false,"given":"Eisaku","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-5184","authenticated-orcid":false,"given":"Jun-Ichiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0310-5302","authenticated-orcid":false,"given":"Takeshi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Department of Oral Infection Medicine, Periodontology, School of Dentistry, Asahi University, 1851 Hozumi, Mizuho 501-0296, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2598-343X","authenticated-orcid":false,"given":"Yoshihiko","family":"Sugita","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"},{"name":"Department of Oral Pathology\/Forensic Odontology, School of Dentistry, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-411X","authenticated-orcid":false,"given":"Akio","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya 464-8651, Aichi, Japan"},{"name":"Division of Molecular Genetics and Immunology, Center for Advanced Oral Science, Aichi Gakuin University, 1-100 Kusumotocho, Chikusa-ku, Nagoya 464-0037, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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