Developmental potency of human ES cell-derived mesenchymal stem cells revealed in mouse embryos following blastocyst injection

Huang, Borong; Fu, Siyi; Hao, Yanan; Yeung, Cheung Kwan; Zhang, Xin; Li, Enqin; Xu, Xiaoling; Shao, Ningyi; Xu, Ren-He

doi:10.1016/j.celrep.2023.113459

Cited by 1 publication

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“…[ 9 , 14 ] To test whether MSCs can modify the response of CTCs to NK cytotoxicity before departure from a primary tumor, we cocultured organoids formed by human primary breast cancer cells [ 33 ] with MSCs derived from the ENVY human embryonic stem cell (hESC) line [ 34 ] in a 3D system. To distinguish the two cell sources, we stained the breast cancer cells with TO‐PRO‐3 (red) in contrast to hESC‐derived MSCs (E‐MSCs), which expresse green fluorescent protein (GFP) [ 35 ] (Figure 1F ). In the presence of E‐MSCs, the cancer cells tended to aggregate in the center of the organoids, while the E‐MSCs lined along the margins (Figure 1F ).…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS‐STING‐IFNβ‐HLA

Yi,

Qin,

Yang

et al. 2024

Advanced Science

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Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer‐associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction‐dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS‐cGAMP‐STING signaling loop, leading to increased production of interferon‐β (IFNβ) by MSCs. IFNβ reversely enhances the type I IFN (IFN‐I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA‐I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN‐I signaling, HLA‐I expression, and NK tolerance in human tumor samples. Thus, the NK‐resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.

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