Bidirectional activation of stem-like programs between metastatic cancer and alveolar type 2 cells within the niche
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Felipe Rodrigues Adam Karoutas Stefanie Ruhland Nick Rabas Tatiana Rizou Stefania Di Blasio Rute Ferreira Vicky Bridgeman Robert Goldstone Miriam L Sopena Joo-Hyeon Lee Luigi Ombrato Ilaria MalanchiAbstract
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.
Journal details
Journal
Developmental Cell
Volume
59
Issue number
18
Pages
2398-2413.e8
Available online
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10.1016/j.devcel.2024.05.020
Europe PubMed Central
38866011
Pubmed
38866011
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The publication was previously a preprint.
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