フルテキストURL ijo_50_1_66.pdf
著者 Lee, Suni| Matsuzaki, Hidenori| Maeda, Megumi| Yamamoto, Shoko| Kumagai-Takei, Naoko| Hatayama, Tamayo| Ikeda, Miho| Yoshitome, Kei| Nishimura, Yasumitsu| Otsuki, Takemi|
抄録 Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.
備考 This is an article published by Spandidos Publications
発行日 2016-11-22
出版物タイトル International Journal of Oncology
50巻
1号
出版者 Spandidos
開始ページ 66
終了ページ 74
ISSN 1019-6439
NCID AA10992511
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
論文のバージョン publisher
PubMed ID 27878235
DOI 10.3892/ijo.2016.3776
Web of Sience KeyUT 000391419200007
関連URL https://doi.org/10.3892/ijo.2016.3776
フルテキストURL ijo_50_6_2024.pdf
著者 Maeda, Megumi| Chen, Ying| Lee, Suni| Kumagai-Takei, Naoko| Yoshitome, Kei| Matsuzaki, Hidenori| Yamamoto, Shoko| Hatayama, Tamayo| Ikeda, Miho| Nishimura, Yasumitsu| Otsuki, Takemi|
抄録 We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.
備考 This is an article published by Spandidos Publications This fulltext availavle in Nov 2017
発行日 2017-05-09
出版物タイトル International Journal of Oncology
50巻
6号
出版者 Spandidos
開始ページ 2024
終了ページ 2032
ISSN 1019-6439
NCID AA10992511
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
論文のバージョン publisher
PubMed ID 28498408
DOI 10.3892/ijo.2017.3991
Web of Sience KeyUT 000402692100010
関連URL https://doi.org/10.3892/ijo.2017.3991
フルテキストURL ijo_49_3_877.pdf
著者 Yamada, Hiroshi| Takeda, Tetsuya| Michiue, Hiroyuki| Abe, Tadashi| Takei, Kohji|
抄録 The endocytic protein dynamin participates in the formation of actin-based membrane protrusions such as podosomes, pseudopodia, and invadopodia, which facilitate cancer cell migration, invasion, and metastasis. However, the role of dynamin in the formation of actin-based membrane protrusions at the leading edge of cancer cells is unclear. In this study, we demonstrate that the ubiquitously expressed dynamin 2 isoform facilitates cell migration by stabilizing F-actin bundles in filopodia of the lung cancer cell line H1299. Pharmacological inhibition of dynamin 2 decreased cell migration and filopodial formation. Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by immunofluorescent and immunoelectron microscopy. Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. Expression of wild-type cortactin rescued the punctate-like localization of dynamin 2 and filopodial formation. The incubation of dynamin 2 and cortactin with F-actin induced the formation of long and thick actin bundles, with these proteins colocalizing at F-actin bundles. A depolymerization assay revealed that dynamin 2 and cortactin increased the stability of F-actin bundles. These results indicate that dynamin 2 and cortactin participate in cell migration by stabilizing F-actin bundles in filopodia. Taken together, these findings suggest that dynamin might be a possible molecular target for anticancer therapy.
発行日 2016-06-30
出版物タイトル International Journal of Oncology
49巻
3号
出版者 Spandidos
開始ページ 877
終了ページ 886
ISSN 1019-6439
NCID AA10992511
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
論文のバージョン publisher
PubMed ID 27572123
DOI 10.3892/ijo.2016.3592
Web of Sience KeyUT 000382447300003
関連URL isVersionOf https://doi.org/10.3892/ijo.2016.3592
フルテキストURL ijo_49_2_499.pdf
著者 Yamada, Chiaki| Aikawa, Tomonao| Okuno, Emi| Miyagawa, Kazuaki| Amano, Katsuhiko| Takahata, Sosuke| Kimata, Masaaki| Okura, Masaya| Iida, Seiji| Kogo, Mikihiko|
抄録 Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.
発行日 2016-05-31
出版物タイトル International Journal of Oncology
49巻
2号
出版者 Spandidos
開始ページ 499
終了ページ 508
ISSN 1019-6439
NCID AA10992511
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
論文のバージョン publisher
PubMed ID 27279422
DOI 10.3892/ijo.2016.3548
Web of Sience KeyUT 000378263600007
関連URL isVersionOf https://doi.org/10.3892/ijo.2016.3548