Macrophage-derived SPARC Attenuates M2-mediated Pro-tumour Phenotypes

Hu, Jiayin; Ma, Yue; Ma, Jiachi; Chen, Shanwen; Zhang, Xiaoqian; Guo, Shuqin; Huang, Zhihao; Yue, Taohua; Yang, Yanpeng; Ning, Yingze; Zhu, Jing; Wang, Pengyuan; Wang, Xin; Chen, Guowei; Liu, Yucun

doi:10.7150/jca.39651

Cited by 17 publications

(8 citation statements)

References 32 publications

(45 reference statements)

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“…However, Hu et al showed that SPARC upregulation in M2-type macrophages can inhibit M2-mediated promotion of growth, migration and antiapoptotic effects in gastric cancer (GC). SPARC is a key tumor suppressor in GC, which demonstrates the high specificity of SPARC in different cancers [32]. Here, we showed that the expression of SPARC was increased in M2-polarized macrophages and TAMs, which is similar to the results of Johannes et al…”

Section: Discussionsupporting

confidence: 91%

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

Deng¹,

Yun²,

Yan³

et al. 2022

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Cholangiocarcinoma (CCA) is a disease that includes a variety of epithelial neoplasms characterized by the differentiation of cholangiocytes. M2 polarization is imperative to the development of CCA cells. In this study, we investigated the influence of secreted protein acidic and rich in cysteine (SPARC) on M2 polarization and CCA cell growth. We found that the SPARC level was amplified in M2-polarized macrophages and TAMs. In addition, the downregulation of SPARC prevented the M2 polarization of macrophages. Silencing SPARC inhibited the M2 macrophage-mediated effects on the proliferation, migration, and angiogenesis of CCA cells.Additionally, SPARC knockdown blocked the M2 polarization of macrophages by inhibiting the PI3K/AKT signaling. Moreover, an activator of PI3K signaling repressed the effect of SPARC knockdown on the M2 macrophage-induced elevation of proliferation, migration, and angiogenesis in CCA cells. In conclusion, SPARC contributes to the M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of CCA cells, which provides new insight into the treatment of CCA.

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Section: Discussionsupporting

confidence: 91%

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

Deng¹,

Yun²,

Yan³

et al. 2022

neo

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“…Also, SPARC-/- mice were shown to mount insufficient innate immune responses [ 130 ]. In addition to tumor cells and fibroblasts, M2 macrophages have been shown to be a major source of SPARC in gastric cancer [ 131 ]. Moreover, this recent study demonstrated that SPARC overexpression in M2 macrophages reduced M2-mediated functions including proliferation of gastric cancer cells, emphasizing the anti-tumorigenic role of SPARC in digestive cancers [ 131 ].…”

Section: Immune Regulation By Ecm Proteins In Digestive Cancersmentioning

confidence: 99%

Stromal Protein-Mediated Immune Regulation in Digestive Cancers

Gamradt

Fouchardière

Hennino

2021

Cancers

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The stromal tumor microenvironment (TME) consists of immune cells, vascular and neural structures, cancer-associated fibroblasts (CAFs), as well as extracellular matrix (ECM), and favors immune escape mechanisms promoting the initiation and progression of digestive cancers. Numerous ECM proteins released by stromal and tumor cells are crucial in providing physical rigidity to the TME, though they are also key regulators of the immune response against cancer cells by interacting directly with immune cells or engaging with immune regulatory molecules. Here, we discuss current knowledge of stromal proteins in digestive cancers including pancreatic cancer, colorectal cancer, and gastric cancer, focusing on their functions in inhibiting tumor immunity and enabling drug resistance. Moreover, we will discuss the implication of stromal proteins as therapeutic targets to unleash efficient immunotherapy-based treatments.

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“…Similarly, the expression of the infected-specific top likelihood genes Cxcl2 , Cd36, and Pdpn was associated with the presence of efferocytic M2-like macrophages ( Figure S5F , green clusters). The distant Sparchi macrophage cluster 5 exhibited C-C chemokine receptor type 7 ( Ccr7 ) exhaustion ( Figure S5F , red clusters), indicating that these cells might be of M1-like origin (Hu et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Decoding the complexity of delayed wound healing followingEnterococcus faecalisinfection

Celik,

Lee,

Tanoto

et al. 2023

Preprint

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Wound infections are highly prevalent, and can lead to delayed or failed healing, causing significant morbidity and adverse economic impacts. These infections occur in various contexts, including diabetic foot ulcers, burns, and surgical sites.Enterococcus faecalisis often found in persistent non-healing wounds, but its contribution to chronic wounds remains understudied. To address this, we employed single-cell RNA sequencing (scRNA-seq) on infected wounds in comparison to uninfected wounds in a mouse model. Examining over 23,000 cells, we created a comprehensive single-cell atlas that captures the cellular and transcriptomic landscape of these wounds. Our analysis revealed unique transcriptional and metabolic alterations in infected wounds, elucidating the distinct molecular changes associated with bacterial infection compared to the normal wound healing process. We identified dysregulated keratinocyte and fibroblast transcriptomes in response to infection, jointly contributing to an anti-inflammatory environment. Notably,E. faecalisinfection prompted a premature, incomplete epithelial-to-mesenchymal transition in keratinocytes. Additionally,E. faecalisinfection modulated M2-like macrophage polarization by inhibiting pro-inflammatory resolutionin vitro,in vivo,and in our scRNA-seq atlas. Furthermore, we discovered macrophage crosstalk with neutrophils, which regulates chemokine signaling pathways, while promoting anti-inflammatory interactions with endothelial cells. Overall, our findings offer new insights into the immunosuppressive role ofE. faecalisin wound infections.AUTHOR SUMMARYWound infections, including diabetic foot ulcers, burns, or surgical sites, often lead to prolonged healing and significant health and economic burdens. Among the bacteria implicated in these persistent wounds,Enterococcus faecalisremains a relatively enigmatic player. To unravel its role in non-healing wounds, we used single-cell RNA sequencing in a mouse model, scrutinizing over 23,000 cells to construct a comprehensive single-cell map of infected wounds compared to uninfected wounds. Our investigation revealed distinct genetic and metabolic alterations in infected wounds, in which infection resulted in a perturbed inflammatory environment delayed wound healing signatures. Specifically,E. faecalisinfection induces a premature and incomplete transition in keratinocytes, impeding their healing function. Furthermore, infection influences the behavior of immune cells like macrophages, affecting the body’s response to the infection. These findings not only shed light onE. faecalis’s role in delayed wound healing but also offer potential avenues for future treatments, providing valuable insights into the challenging realm of wound infections.

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Macrophage-derived SPARC Attenuates M2-mediated Pro-tumour Phenotypes

Cited by 17 publications

References 32 publications

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

Stromal Protein-Mediated Immune Regulation in Digestive Cancers

Decoding the complexity of delayed wound healing followingEnterococcus faecalisinfection

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