非依賴型HDGF與TNF-alpha信號對於幽門螺旋桿菌感染人胃癌類器官的研究
非依賴型HDGF與TNF-alpha信號對於幽門螺旋桿菌感染人胃癌類器官的研究
我們製備了人類3-D胃癌類器官研究幽門螺旋桿菌 (H. pylori) 的致瘤性和細胞毒性之間的相關性。此外還檢測肝細胞瘤衍生生長因子 (HDGF) 和腫瘤壞死因子 (TNF-α) 對幽門螺旋桿菌感染胃癌類器官生長和侵襲活性的影響。以細胞毒素相關基因A (CagA)-綠色螢光蛋白 (GFP) 標記的幽門螺旋桿菌用於追踪胃類器官的感染。來自不同幽門螺旋桿菌物種的 Cag 編碼毒素的細胞毒性並不影響每個幽門螺旋桿菌感染之癌症類器官的增殖。為了釐清從幽門螺旋桿菌感染癌症類器官所分泌的 HDGF 和 TNF-α作用，我們製備了重組 HDGF 和 TNF-α 並測量胃癌類器官的細胞毒性和侵襲性。HDGF 以 H. pylori 的物種特異性方式控制每個類器官的生長，但 TNF-α 降低H. pylori 感染癌症類器官的細胞活力。 此外HDGF 以物種依賴性方式控制幽門螺旋桿菌感染癌症類器官的侵襲活性。然而TNF-α 降低大多數類器官的侵襲活動。我們證明在幽門螺旋桿菌感染期間人類胃類器官響應 HDGF 和 TNFα 的不同細胞毒性和侵襲信號。重組HDGF和TNF-α對H. pylori感染胃癌的發生和侵襲具有不同的抑制作用。因此我們提出 HDGF 和 TNF-α 是幽門螺旋桿菌感染胃癌發展的非依賴型信號。3-D 類器官培養系統中的生長因子信號傳導與2-D癌細胞中的不同。
【應用與亮點】
我們團隊致力於開發用於研究細菌感染的 3D 胃類器官新治療平台。
【研究團隊】
團隊成員：橫山一成教授, 吳登強教授, 郭昭宏教授, 戴明泓教授
代表單位：再生醫學與細胞治療研究中心
團隊簡介：我們團隊確定了該定義因子以不同方式激活 HOXA 基因家族的機制。在胃癌的發展過程中，我們使用由幽門螺旋桿菌誘導的胃類器官。我們在 3D 類器官系統上使用 BMP 家族獲得了一種新的癌症幹細胞療法，可以防止胃癌的發展。
聯繫方式：dechwu@kmu.edu.tw (D.-C.W.); kazu@kmu.edu.tw (K.K.Y.)
期刊發表: Int. J. Mol. Sci. 2023, 24, 6567.
論文連結: https://doi.org/10.3390/ijms24076567
Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by Helicobacter pylori
Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by Helicobacter pylori
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNF)-α on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNF-α secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNF-α and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNF-α decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNF-α decreased the invasion activities of most organoids. We demonstrated different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNF-α during infection by H. pylori. Recombinant HDGF and TNF-α inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNF-α are independent signals for the development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.
Application and Highlights:
The team committed to develop the new therapeutic platform of 3D gastric organoids for studying bacterial infection.
Research Team Members:Dr. Kazunari K. Yokoyama,Dr. Deng-Chyang Wu,Dr. Chao-Hung Kuo,Dr. Ming-Hong Tai
Representative Department:Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University
Introduction of Research Team:
Our teams identified the mechanism via which this defined factor activates the HOXA gene family differently. In development of gastric cancers, were using gastric organoids that induced by Helicobacter pylori (H. P.). We obtained a new potential CSC therapy using BMP family on the 3D-organoid system to protect against the development of gastric cancer.
Contact Email:
dechwu@kmu.edu.tw (D.-C.W.); kazu@kmu.edu.tw (K.K.Y.);
Publication:
Int. J. Mol. Sci. 2023, 24, 6567.
Full-Text Article:
https://doi.org/10.3390/ijms24076567
