Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Anticancer Res. 2023 Oct;43(10):4359-4364. doi: 10.21873/anticanres.16631.
BACKGROUND/AIM: Intra-tumoral heterogeneity, which is frequently found in various types of cancers, has been suggested to play an important role in cancer progression and metastasis. The findings of our previous study suggested that p-SMAD2 and c-MET signaling might play important roles in the progression to lymph node metastasis of HER2-positive gastric cancer. In this study, we confirmed the effect of SMAD2/MET signaling in the progression of HER2-positive gastric cancer in an animal model.
NCI-N87 cells over-expressing ERBB2, SMAD2, MET were used. To confirm the role of SMAD2 and MET expression on lymph node metastasis of gastric cancer, we orthotopically injected NCI-N87 cells with or without the knockdown of both SMAD2 and MET into the gastric walls of BALBc nude mice.
The number of metastatic lymph nodes was significantly smaller in the knockdown group compared to that in the control group. However, there was no significant difference in gastric tumor size between the two groups.
SMAD2 and MET signaling might play important roles specifically in the progression to lymph node metastasis of HER2-positive gastric cancer. c-MET and SMAD2 may be useful targets for preventing lymph node metastasis in patients with HER2-positive gastric cancer.
背景/目的：在各种类型的癌症中经常发现肿瘤内异质性，据推测其在癌症进展和转移中发挥着重要作用。我们之前的研究结果表明，p-SMAD2 和 c-MET 信号可能在 HER2 阳性胃癌向淋巴结转移的进展中发挥重要作用。在这项研究中，我们在动物模型中证实了 SMAD2/MET 信号在 HER2 阳性胃癌进展中的作用。
使用过表达 ERBB2、SMAD2 和 MET 的 NCI-N87 细胞。为了确认 SMAD2 和 MET 表达对胃癌淋巴结转移的作用，我们将敲低 SMAD2 和 MET 的 NCI-N87 细胞或对照细胞原位注射到 BALBc 裸鼠的胃壁中。
与对照组相比，敲低组的转移淋巴结数量明显减少。然而，两组的胃肿瘤大小无显著差异。
SMAD2 和 MET 信号可能在 HER2 阳性胃癌向淋巴结转移的进展中发挥重要作用。c-MET 和 SMAD2 可能是预防 HER2 阳性胃癌患者淋巴结转移的有用靶点。
