A specific anti-cyclin D1 intrabody represses breast cancer cell proliferation by interrupting the cyclin D1–CDK4 interaction

Zhao, Jialiang; Wu, Yan; Xiao, Tao; Cheng, Cheng; Zhang, Tong; Gao, Ziyang; Hu, Siyuan; Ren, Ze; Yu, Xinze; Yang, Fang; Li, Guiying

doi:10.1007/s10549-023-06866-7

Cited by 3 publications

(3 citation statements)

References 50 publications

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“…Moreover, antibodies that clearly work in advanced colon cancer through a signaling blockade during angiogenesis did not show relevant benefits in patients with pancreatic cancer. To overcome the limitation of desirable intracellular signaling blockades in tumor cells, intrabodies have been designed that are capable of targeting intracellular tumor-associated antigens and neoantigens in cells and xenograft mouse models [27,29,[51][52][53][54][55][56][57][58][59][60]. This strongly supports the further development of relevant intrabodies, with the goal of setting up clinical trials.…”

Section: Discussionmentioning

confidence: 89%

TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth

Ajay,

Gasser,

Hsiao

et al. 2024

Antibodies

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Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) remains a deadly cancer worldwide with a need for new therapeutic approaches. A dysregulation in the equilibrium between pro- and anti-inflammatory responses with a predominant immunosuppressive inflammatory reaction in advanced stage tumors seem to contribute to tumor growth and metastasis. The current therapies do not include strategies against pro-tumorigenic inflammation in cancer patients. We have shown that the upregulated cell surface expression of Toll-like Receptor (TLR) 2 and of TLR9 inside PDAC cells maintain chronic inflammatory responses, support chemotherapeutic resistance, and mediate tumor progression in human pancreatic cancer. We further demonstrated intracellular TLR2 and TLR9 targeting using specific intrabodies, which resulted in downregulated inflammatory signaling. In this study, we tested, for the first time, an intrabody-mediated TLR blockade in human TLR2- and TLR9-expressing pancreatic cancer cells for its effects on inflammatory signaling-mediated tumor growth. Newly designed anti-TLR2- and anti-TLR9-specific intrabodies inhibited PDAC growth. Co-expression analysis of the intrabodies and corresponding human TLRs showed efficient retention and accumulation of both intrabodies within the endoplasmic reticulum (ER), while co-immunoprecipitation studies indicated both intrabodies interacting with their cognate TLR antigen within the pancreatic cancer cells. Cancer cells with attenuated proliferation expressing accumulated TLR2 and TRL9 intrabodies demonstrated reduced STAT3 phosphorylation signaling, while apoptotic markers Caspases 3 and 8 were upregulated. To conclude, our results demonstrate the TLR2 and TLR9-specific intrabody-mediated signaling pathway inhibition of autoregulatory inflammation inside cancer cells and their proliferation, resulting in the suppression of pancreatic tumor cell growth. These findings underscore the potential of specific intrabody-mediated TLR inhibition in the ER relevant for tumor growth inhibition and open up a new therapeutic intervention strategy for the treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 89%

TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth

Ajay,

Gasser,

Hsiao

et al. 2024

Antibodies

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“…Cyclin D1 is recognized as a crucial indicator of cell proliferation and serves as a pivotal regulator of cell cycle checkpoints governing G2/M and G1/S transitions [ 32 , 33 ]. Upon cell cycle initiation, cyclin D1 is rapidly upregulated, facilitating the division and replication of prostate stromal and epithelial cells [ 34 , 35 ]. Cyclin D1 functions as a vital sensor and integrator of extracellular signals in normal physiological processes, modulating cellular activities by binding to cyclin-dependent kinases [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Xu,

Cao,

Zhang

et al. 2024

Marine Drugs

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Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

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“…For antigen-antibody interactions, the three-dimensional structure of the Fab region is crucial. The charge of the amino acids as well as the amino acid sequence in the Fab region define the structure [14,48]. Entropic and enthalpic effects work together to determine the affinity of antigen-antibody interactions.…”

Section: Fluorescent Label Conjugated Antibodiesmentioning

confidence: 99%

Flow cytometry: Aspects and application in plant and biological science

Jyoti,

Chandel,

Singh

2023

Journal of Biophotonics

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Flow cytometry is a potent method that enables the quick and concurrent investigation of several characteristics of single cells in solution. Photodiodes or photomultiplier tubes are employed to detect the dispersed and fluorescent light signals that are produced by the laser beam as it passes through the cells. Photodetectors transform the light signals produced by the laser into electrical impulses. A computer then analyses these electrical impulses to identify and measure the various cell populations depending on their fluorescence or light scattering characteristics. Based on their fluorescence or light scattering properties, cell populations can be examined and/or isolated. This review covers the basic principle, components, working and specific biological applications of flow cytometry, including studies on plant, cell and molecular biology and methods employed for data processing and interpretation as well as the potential future relevance of this methodology in light of retrospective analysis and recent advancements in flow cytometry.

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A specific anti-cyclin D1 intrabody represses breast cancer cell proliferation by interrupting the cyclin D1–CDK4 interaction

Cited by 3 publications

References 50 publications

TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth

TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Flow cytometry: Aspects and application in plant and biological science

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