Reprogramming of tumor-associated macrophages by metabolites generated from tumor microenvironment

Kim, Seung Woo; Kim, Chan Woo; Moon, Young-Ah; Kim, Hong Seok

doi:10.1080/19768354.2024.2336249

Cited by 2 publications

(1 citation statement)

References 190 publications

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“…Extracellular vesicles (EVs) are cell-derived membrane vesicles, which include exosomes originating from intraluminal vesicles and microvesicles shed from the plasma membrane (Colombo et al 2014 ; van Niel et al 2018 ). EVs carry various cellular components, including lipids, nucleic acids, and proteins, and upon uptake by their target cells, they can deliver these components, serving as an effective tool of intercellular communication in many physiological and pathological processes (Zaborowski et al 2015 ; Kalluri and LeBleu 2020 ; Kita and Shimomura 2022 ; Kim et al 2024 ). Due to their inherent in vivo delivery capabilities, numerous attempts have been made to utilize EVs as a gene, protein, or drug delivery platform for therapeutic purposes (Wiklander et al 2019 ; Herrmann et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion

Lee,

Kim

et al. 2024

Animal Cells and Systems

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Extracellular vesicles (EVs), transporting diverse cellular components, play a crucial role in intercellular communication in numerous physiological and pathological processes. EVs have also been recognized as a drug delivery platform for therapeutic purposes and cell-free regenerative medicine. While various approaches have focused on increasing EV production for efficient use therapeutic use of EVs, enhancing the quality of EVs, such as ensuring efficient uptake by their target cells, has not been widely explored. In this study, we linked a negative membrane curvature-forming inverse BAR (IBAR) domain with an integrin β tail-binding talin F3 domain to create the IBAR-F3 fusion protein. We observed that IBAR-F3 can trigger filopodia-like membrane protrusions and attract integrins to those protrusion-rich regions, when expressed in Chinese hamster ovary cells expressing integrin αIIbβ3. Surprisingly, the expression of IBAR-F3 also induced a robust production of EVs, which were then efficiently taken up by nearby cells in an integrin-dependent manner. Moreover, IBAR triggered integrin activation, presumably by inducing negative membrane curvature that likely disrupts the interaction between the integrin α and β transmembrane domain. Therefore, we suggest that IBAR-F3 should be utilized to promote both EV production and efficient uptake mediated by integrins. Furthermore, the negative curvature-inducing integrin activation suggests that integrins on EVs can be activated by the nanoscale change in the curvature of the EV without the need for conventional machinery to activate integrin inside the EVs.

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Section: Introductionmentioning

confidence: 99%

Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion

Lee,

Kim

et al. 2024

Animal Cells and Systems

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The spatial distribution of intermediate fibroblasts and myeloid-derived cells dictate lymph node metastasis dynamics in oral cancer

Shaikh,

Dhar,

Moorthy

et al. 2024

J Transl Med

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Background Oral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis. Methods We collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME. Results We found that the tumor–stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation. Conclusion We have generated a functional organization of the tumor–stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-024-05511-1.

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Reprogramming of tumor-associated macrophages by metabolites generated from tumor microenvironment

Cited by 2 publications

References 190 publications

Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion

Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion

The spatial distribution of intermediate fibroblasts and myeloid-derived cells dictate lymph node metastasis dynamics in oral cancer

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