LSR antibody promotes apoptosis and disrupts epithelial barriers via signal pathways in endometrial cancer

Saito, Koko; Konno, Takumi; Kohno, Takayuki; Shimada, Hiroshi; Matsuura, Motoki; Okada, Tadahi; Kura, Arisa; Ishii, Daichi; Kondoh, Masuo; Saito, Tsuyoshi; Kojima, Takashi

doi:10.1080/21688370.2022.2106113

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…Moreover, in 2004, a molecular therapy targeting HER-2, incorporating active caspase domains and the cytotoxic domain of P. aeruginosa (the same employed in T22-PE24-H6) was successful in preclinical experiments but, as far as we know, it did not reach clinical trials [24][25][26]. Recently, antitumor the effect of angubindin-1 (derived from C. perfingens iota toxin) has been evaluated in vitro, but no preclinical in vivo or clinical results have been published to date [27,28].…”

Section: Discussionmentioning

confidence: 99%

Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models

Medina-Gutiérrez

García-León

Gallardo

et al. 2022

Cancers

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Patients with advanced endometrial cancer (EC) show poor outcomes. Thus, the development of new therapeutic approaches to prevent metastasis development in high-risk patients is an unmet need. CXCR4 is overexpressed in EC tumor tissue, epitomizing an unexploited therapeutic target for this malignancy. The in vitro antitumor activity of two CXCR4-targeted nanoparticles, including either the C. diphtheriae (T22-DITOX-H6) or P. aeruginosa (T22-PE24-H6) toxin, was evaluated using viability assays. Apoptotic activation was assessed by DAPI and caspase-3 and PARP cleavage in cell blocks. Both nanotoxins were repeatedly administrated to a subcutaneous EC mouse model, whereas T22-DITOX-H6 was also used in a highly metastatic EC orthotopic model. Tumor burden was assessed through bioluminescence, while metastatic foci and toxicity were studied using histological or immunohistochemical analysis. We found that both nanotoxins exerted a potent antitumor effect both in vitro and in vivo via apoptosis and extended the survival of nanotoxin-treated mice without inducing any off-target toxicity. Repeated T22-DITOX-H6 administration in the metastatic model induced a dramatic reduction in tumor burden while significantly blocking peritoneal, lung and liver metastasis without systemic toxicity. Both nanotoxins, but especially T22-DITOX-H6, represent a promising therapeutic alternative for EC patients that have a dismal prognosis and lack effective therapies.

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Section: Discussionmentioning

confidence: 99%

Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models

Medina-Gutiérrez

García-León

Gallardo

et al. 2022

Cancers

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Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine

An,

Wang,

Wang

et al. 2024

EMBO J

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The identification of host factors with antiviral potential is important for developing effective prevention and therapeutic strategies against SARS-CoV-2 infection. Here, by using immortalized cell lines, intestinal organoids, ex vivo intestinal tissues and humanized ACE2 mouse model as proof-of-principle systems, we have identified lipolysis-stimulated lipoprotein receptor (LSR) as a crucial host defense factor against SARS-CoV-2 infection in the small intestine. Loss of endogenous LSR enhances ACE2-dependent infection by SARS-CoV-2 Spike (S) protein-pseudotyped virus and authentic SARS-CoV-2 virus, and exogenous administration of LSR protects against viral infection. Mechanistically, LSR interacts with ACE2 both in cis and in trans, preventing its binding to S protein, and thus inhibiting viral entry and S protein-mediated cell–cell fusion. Finally, a small LSR-derived peptide blocks S protein binding to the ACE2 receptor in vitro. These results identify both a previously unknown function for LSR in antiviral host defense against SARS-CoV-2, with potential implications for peptide-based pan-variant therapeutic interventions.

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The roles of tight junction protein cingulin in human endometrioid endometrial cancer

Kura,

Saito,

Konno

et al. 2024

Tissue Barriers

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LSR antibody promotes apoptosis and disrupts epithelial barriers via signal pathways in endometrial cancer

Cited by 4 publications

References 40 publications

Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models

Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models

Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine

The roles of tight junction protein cingulin in human endometrioid endometrial cancer

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