Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2023 Mar 31;24(7):6567. doi: 10.3390/ijms24076567.
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of (). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of -infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of did not affect the proliferation of each -infected cancer organoid. To clarify the role of HDGF and TNFα secreted from -infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of , but TNFα decreased the cell viability in -infected cancer organoids. Furthermore, HDGF controlled the invasion activity of -infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by . Recombinant HDGF and TNFα inhibited the development and invasion of -infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of -infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.
我们制备了人胃癌的三维（3-D）类器官，并研究了（）的致瘤性和细胞毒性之间的相关性。此外，还研究了肝癌衍生生长因子（HDGF）和肿瘤坏死因子（TNFα）对感染的胃癌类器官生长和侵袭活性的影响。细胞毒素相关基因 A（CagA）-绿色荧光蛋白（GFP）标记的用于追踪胃类器官中的感染。来自不同种属的 Cag 编码毒素的细胞毒性并不影响每个感染的癌症类器官的增殖。为了阐明 HDGF 和 TNFα 的作用，这些因子由感染的癌症类器官分泌，我们制备了重组 HDGF 和 TNFα，并测量了胃癌类器官的细胞毒性和侵袭性。HDGF 以物种特异性的方式控制每个类器官的生长，但 TNFα 降低了感染的癌症类器官中的细胞活力。此外，HDGF 以物种依赖的方式控制感染的癌症类器官的侵袭活性。然而，TNFα 降低了大多数类器官的侵袭活性。我们发现，在被感染期间，人类胃类器官对 HDGF 和 TNFα 的细胞毒性和侵袭性有不同的信号转导。重组 HDGF 和 TNFα 以不同的方式抑制感染的胃癌的发展和侵袭。因此，我们提出 HDGF 和 TNFα 是感染的胃癌发展的独立信号。生长因子在 3-D 类器官培养系统中的信号转导与在二维癌细胞中的信号转导不同。
