Abstract：
A key step for metastatic outgrowth involves the generation of a deeply altered microenvironment (niche) that supports the malignant behavior of cancer cells. The complexity of the metastatic niche has posed a significant challenge in elucidating the underlying programs driving its origin. Here, by focusing on early stages of breast cancer metastasis to the lung in mice, we describe a cancer-dependent chromatin remodeling and activation of developmental programs in alveolar type 2 (AT2) cells within the niche. We show that metastatic cells can prime AT2 cells into a reprogrammed multilineage state. In turn, this cancer-induced reprogramming of AT2 cells promoted stem-like features in cancer cells and enhanced their initiation capacity. In conclusion, we propose the concept of \"reflected stemness\" as an early phenomenon during metastatic niche initiation, wherein metastatic cells reprogram the local tissue into a stem-like state that enhances intrinsic cancer-initiating potential, creating a positive feedback loop where tumorigenic programs are amplified.
摘要：
转移性生长的关键步骤涉及产生支持癌细胞恶性行为的深度改变的微环境（生态位）。转移性生态位的复杂性在阐明驱动其起源的基础程序方面提出了重大挑战。这里,通过关注乳腺癌转移到小鼠肺部的早期阶段，我们描述了小生境内肺泡2型（AT2）细胞中癌症依赖性染色质重塑和发育程序的激活。我们表明转移细胞可以使AT2细胞进入重编程的多谱系状态。反过来,这种癌症诱导的AT2细胞重编程促进了癌细胞的干细胞样特征并增强了其启动能力.总之,我们提出了“反射干性”的概念，作为转移生态位启动过程中的早期现象，其中转移细胞将局部组织重新编程为茎样状态，从而增强内在的癌症启动潜力，创建一个正反馈循环，其中肿瘤的程序被放大。
