胶原蛋白XVII通过与肿瘤微环境的相互作用，在胰腺癌中调节肿瘤生长。
Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment.
发表日期：2023 Sep 08
作者：
Ryosuke Kashiwagi, Ryo Funayama, Shuichi Aoki, Aya Matsui, Sebastian Klein, Yukihiro Sato, Tsubasa Suzuki, Keigo Murakami, Koetsu Inoue, Masahiro Iseki, Kunihiro Masuda, Masamichi Mizuma, Hisamichi Naito, Dan G Duda, Michiaki Unno, Keiko Nakayama
来源：
GENES & DEVELOPMENT
摘要：
结缔17型胶原基因（COL17A1）在肿瘤组织中的表达与患者的存活率呈正相关或负相关，取决于癌症类型。因此，高COL17A1的表达是乳腺癌的良性预后标志物，但是对胰腺癌是不利的。本研究探讨了COL17A1表达对胰腺肿瘤生长及其基础机制的影响。对人胰腺癌组织的已发表的单细胞RNA测序数据进行分析表明，COL17A1主要在癌细胞而非周围基质细胞中表达。在体外，COL17A1的强制表达并未显著影响小鼠胰腺癌细胞株KPC和AK4.4的增殖速率。然而，在小鼠同源移植瘤模型中，分别注射KPC或AK4.4细胞至同系C57BL/6或FVB小鼠体内，COL17A1的表达促进或抑制肿瘤生长，这表明COL17A1对肿瘤生长的影响受肿瘤微环境的影响。对肿瘤组织的RNA测序分析显示COL17A1对基因表达谱有影响（包括与细胞增殖、免疫应答、Wnt信号和Hippo信号相关的基因表达），在C57BL/6-KPC和FVB-AK4.4肿瘤中有差异。因此，我们的数据表明COL17A1以肿瘤细胞与肿瘤微环境相互作用为基础，促进或抑制癌症进展。© 2023 The Authors. 由John Wiley & Sons Australia, Ltd代表日本癌症协会出版的《癌症科学》发布。
Expression of the gene for collagen XVII (COL17A1) in tumor tissue is positively or negatively associated with patient survival depending on cancer type. High COL17A1 expression is thus a favorable prognostic marker for breast cancer but unfavorable for pancreatic cancer. This study explored the effects of COL17A1 expression on pancreatic tumor growth and their underlying mechanisms. Analysis of published single-cell RNA-sequencing data for human pancreatic cancer tissue revealed that COL17A1 was expressed predominantly in cancer cells rather than surrounding stromal cells. Forced expression of COL17A1 did not substantially affect the proliferation rate of the mouse pancreatic cancer cell lines KPC and AK4.4 in vitro. However, in mouse homograft tumor models in which KPC or AK4.4 cells were injected into syngeneic C57BL/6 or FVB mice, respectively, COL17A1 expression promoted or suppressed tumor growth, respectively, suggesting that the effect of COL17A1 on tumor growth was influenced by the tumor microenvironment. RNA-sequencing analysis of tumor tissue revealed effects of COL17A1 on gene expression profiles (including the expression of genes related to cell proliferation, the immune response, Wnt signaling, and Hippo signaling) that differed between C57BL/6-KPC and FVB-AK4.4 tumors. Our data thus suggest that COL17A1 promotes or suppresses cancer progression in a manner dependent on the interaction of tumor cells with the tumor microenvironment.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.