Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Nat Commun. 2024 Aug 28;15(1):7414. doi: 10.1038/s41467-024-51450-2.
How prostate cancer cells and their precursors mediate changes in the tumor microenvironment (TME) to drive prostate cancer progression is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we perform extensive single-cell RNA-sequencing (scRNA-seq) and molecular pathology of the comparative biology between human prostate cancer and key stages in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues reveal that cancer cell-intrinsic activation of MYC signaling is a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Cell communication network and pathway analyses in GEMMs show that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogram the TME during carcinogenesis, leading to a convergence of cell state alterations in neighboring epithelial, immune, and fibroblast cell types that parallel key findings in human prostate cancer.
前列腺癌细胞及其前体细胞如何介导肿瘤微环境（TME）的变化以推动前列腺癌的进展尚不清楚，部分原因是无法在人体组织中对疾病的演变进行纵向研究。为了克服这一限制，我们对人类前列腺癌和前列腺癌基因工程小鼠模型（GEMM）疾病演变的关键阶段之间的比较生物学进行了广泛的单细胞 RNA 测序（scRNA-seq）和分子病理学研究。我们对人类组织的研究表明，MYC 信号转导的癌症细胞内在激活是人类前列腺癌众所周知的分子和病理学异质性的共同特征。GEMM 中的细胞通讯网络和途径分析表明，MYC 癌基因表达的肿瘤细胞在致癌过程中直接和间接地重塑 TME，导致邻近上皮细胞、免疫细胞和成纤维细胞类型的细胞状态改变趋同，与人类前列腺癌的关键发现相平行。
