Abstract：
Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.
摘要：
肿瘤微环境中的肿瘤-基质相互作用和基质异质性是影响进展的关键因素。转移,和胰腺导管腺癌（PDAC）的化学耐药性。这里,我们使用空间转录组技术,利用PDAC小鼠模型(LSL-KrasG12D/+;LSL-Trp53R172H/+;和Pdx-1-Cre小鼠),对生物活性黑磷纳米材料(生物活性BP)治疗后原发性PDAC和肝转移性PDAC的基因表达情况进行了分析.生物信息学和生化分析表明，生物活性BP通过抑制癌症相关成纤维细胞（CAF）的激活而有助于肿瘤-基质的相互作用。我们的结果表明，生物活性BP有助于CAF异质性通过减少炎性CAF和肌纤维母细胞CAF的量，两个CAF亚群。我们的研究证明了生物活性BP对肿瘤-基质相互作用和CAF异质性的影响，并建议生物活性BP作为潜在的PDAC治疗。
