Signal transducer and activator of transcription 3 downregulation in J774A.1 cell line as a model of M2 macrophages in tumor microenvironment

Seyedi, Zahra; Hashemzadeh, Mohammad Reza; Colagar, Abasalt Hosseinzadeh; Jaafari, Mahmoud Reza

doi:10.4103/0973-1482.187298

Cited by 5 publications

References 32 publications

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Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics

Wan

Chen

et al. 2020

Bioconjugate Chem.

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Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The in vitro results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. In vivo results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.

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Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics

Wan

Chen

et al. 2020

Bioconjugate Chem.

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Tumor-associated macrophage enhances PD-L1-mediated immune escape of bladder cancer through PKM2 dimer/STAT3 complex nuclear translocation

Yu,

Liang,

Xie

et al. 2023

Preprint

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Background Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME) and strongly associated with poor prognosis and drug resistance, including immune checkpoint blockade (ICB) in solid tumor patients. However, the mechanism by which TAM affects immune metabolism reprogramming and immune checkpoint signaling pathway in the bladder cancer (BLCA) TME remains elusive. Methods We analyzed the TCGA cohort of BLCA patients in relation to M2-TAMs signature genes as well as PD-L1 expression, and then explored the cellular and molecular roles by RNA sequencing on constructed BLCA cells with M2-TAMs co-culture systems. we used nucleoplasmic separation and protein cross-linking to search for mechanisms related to tumor metabolism and immune reprogramming following crosstalk effects of M2-TAMs, and constructed a mouse model of BLCA with a high occupancy rate of M2-TAMs and a group of organoids derived from human BLCA fresh tissues to validate therapeutic efficacy of the targets in vivo and in vitro. Results Transforming growth factor-beta (TGF-β) secreted by M2-TAMs increased the level of glycolysis and was involved in PD-L1-mediated immune escape through pyruvate kinase isoenzyme type M2 (PKM2) in the malignant BLCA microenvironment. TGF-β promoted the nuclear translocation of PKM2 dimers in conjunction with phosphorylated signal transducer and activator of transcription (p-STAT3), which exerts its kinase activity, and subsequently promotes PD-L1 expression through the transcription factor role of STAT3. Moreover, the high secretion level of TGF-β activated the JAK2/STAT3 signaling pathway to upregulate PD-L1 expression in BLCA. In vivo, SB-431542 (a TGF-β blocker) and shikonin (a PKM2 inhibitor) significantly reduced PD-L1 expression and inhibited BLCA growth by increasing immune infiltration. In addition, SB-431542 and shikonin inhibited the growth of bladder carcinoma organoids. Conclusions Our work sheds new light on that M2-TAM-derived TGF-β promotes PD-L1-mediated immune evasion in BLCA by increasing the PKM2/STAT3 complex nuclear translocation. Targeting TGF-β receptor blockade and PKM2 inhibition significantly reduces BLCA progression and immunosuppression, and their combination provides a promising target for the treatment of BLCA.

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Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

Seyedi¹,

Amiri

Mohammadzadeh

et al. 2023

JFB

Self Cite

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Among scaffolds used in tissue engineering, natural biomaterials such as plant-based materials show a crucial role in cellular function due to their biocompatibility and chemical indicators. Because of environmentally friendly behavior and safety, green methods are so important in designing scaffolds. A key bioactive flavonoid of the Epimedium plant, Icariin (ICRN), has a broad range of applications in improving scaffolds as a constant and non-immunogenic material, and in stimulating the cell growth, differentiation of chondrocytes as well as differentiation of embryonic stem cells towards cardiomyocytes. Moreover, fusion of ICRN into the hydrogel scaffolds or chemical crosslinking can enhance the secretion of the collagen matrix and proteoglycan in bone and cartilage tissue engineering. To scrutinize, in various types of cancer cells, ICRN plays a decisive role through increasing cytochrome c secretion, Bax/Bcl2 ratio, poly (ADP-ribose) polymerase as well as caspase stimulations. Surprisingly, ICRN can induce apoptosis, reduce viability and inhibit proliferation of cancer cells, and repress tumorigenesis as well as metastasis. Moreover, cancer cells no longer grow by halting the cell cycle at two checkpoints, G0/G1 and G2/M, through the inhibition of NF-κB by ICRN. Besides, improving nephrotoxicity occurring due to cisplatin and inhibiting multidrug resistance are the other applications of this biomaterial.

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Signal transducer and activator of transcription 3 downregulation in J774A.1 cell line as a model of M2 macrophages in tumor microenvironment

Cited by 5 publications

References 32 publications

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics

Tumor-associated macrophage enhances PD-L1-mediated immune escape of bladder cancer through PKM2 dimer/STAT3 complex nuclear translocation

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

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