Targeted destruction of follicle stimulating hormone receptor-positive cancer cells in vitro and in vivo by a lytic peptide Phor21-FSHβ conjugate.
1/5 보강
[BACKGROUND] Extragonadal follicle-stimulating hormone (FSH) receptor (FSHR) expression in various cancers and their endothelial vessel cells has highlighted novel opportunities for targeted FSHR ther
APA
Rahman NA, Chrusciel M, et al. (2025). Targeted destruction of follicle stimulating hormone receptor-positive cancer cells in vitro and in vivo by a lytic peptide Phor21-FSHβ conjugate.. Molecular medicine (Cambridge, Mass.), 31(1), 224. https://doi.org/10.1186/s10020-025-01292-5
MLA
Rahman NA, et al.. "Targeted destruction of follicle stimulating hormone receptor-positive cancer cells in vitro and in vivo by a lytic peptide Phor21-FSHβ conjugate.." Molecular medicine (Cambridge, Mass.), vol. 31, no. 1, 2025, pp. 224.
PMID
40490708 ↗
Abstract 한글 요약
[BACKGROUND] Extragonadal follicle-stimulating hormone (FSH) receptor (FSHR) expression in various cancers and their endothelial vessel cells has highlighted novel opportunities for targeted FSHR therapy.
[METHODS] We investigated the specificity/cytotoxicity of Phor21 fusion lytic peptide, conjugated to 12 different FSHβ-chain fragments to ablate FSHR-expressing cancer cells in vitro and Additionally, the use of the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix (CTX) alone or with the Phor21-FSHβ33-53 C/S conjugate for anticancer therapy was analyzed.
[RESULTS] Phor21 linked to the FSHβ33–53 fragment with cysteine (Cys) replaced by serine (Ser) (Phor21-FSHβ33-53 C/S) demonstrated the highest specific cytotoxicity towards FSHR possessing cancer cells vs. other compounds. Recombinant human FSH treatment significantly decreased the cytotoxicity of Phor21-FSHβ33-53 C/S conjugate in FSHR-positive cancer cells. Phor21-FSHβ33-53 C/S (further addressed as Phor21-FSHβ) treatment in vivo significantly inhibited the growth of FSHR-positive cancer xenografts, resulting in necrosis. The efficacy of the Phor21-FSHβ was enhanced by co-treatment with the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix (CTX). CTX alone exerted pro-apoptotic effects. CTX significantly inhibited the growth of prostate cancer LNCaP cell xenografts. Although FSHR-positive tumor vessel endothelial cells were previously reported in LNCaP cell xenografts, we were unable to reproduce FSHR expression. Consequently, Phor21-FSHβ had no effect on tumor destruction because of the lack of transcripts in the endothelium of these tumor vessel cells.
[CONCLUSION] This novel functional evidence shows that any cancer cell expressing FSHR can be specifically targeted and destroyed by the conjugated lytic peptide Phor21-FSHβ33–53 (Phor21-FSHβ). FSHR expression was not detected in the tumor vessel endothelial cells, which needs further re-evaluation.
[GRAPHICAL ABSTRACT] Schematic overview of the Phor21-FSHb33-53C/S (Phor21-FSHβ) conjugate or CTX specifically targeted to kill FSHR-positive cancer cells. (Figure created using BioRender.com). Phor21-FSHb33-53C/S conjugate, Phor21 lytic backbone conjugated with a native or modified fragment of the FSHb subunit (FSHb33-53); CTX, GnRH antagonist cetrorelix [Image: see text]
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s10020-025-01292-5.
[METHODS] We investigated the specificity/cytotoxicity of Phor21 fusion lytic peptide, conjugated to 12 different FSHβ-chain fragments to ablate FSHR-expressing cancer cells in vitro and Additionally, the use of the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix (CTX) alone or with the Phor21-FSHβ33-53 C/S conjugate for anticancer therapy was analyzed.
[RESULTS] Phor21 linked to the FSHβ33–53 fragment with cysteine (Cys) replaced by serine (Ser) (Phor21-FSHβ33-53 C/S) demonstrated the highest specific cytotoxicity towards FSHR possessing cancer cells vs. other compounds. Recombinant human FSH treatment significantly decreased the cytotoxicity of Phor21-FSHβ33-53 C/S conjugate in FSHR-positive cancer cells. Phor21-FSHβ33-53 C/S (further addressed as Phor21-FSHβ) treatment in vivo significantly inhibited the growth of FSHR-positive cancer xenografts, resulting in necrosis. The efficacy of the Phor21-FSHβ was enhanced by co-treatment with the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix (CTX). CTX alone exerted pro-apoptotic effects. CTX significantly inhibited the growth of prostate cancer LNCaP cell xenografts. Although FSHR-positive tumor vessel endothelial cells were previously reported in LNCaP cell xenografts, we were unable to reproduce FSHR expression. Consequently, Phor21-FSHβ had no effect on tumor destruction because of the lack of transcripts in the endothelium of these tumor vessel cells.
[CONCLUSION] This novel functional evidence shows that any cancer cell expressing FSHR can be specifically targeted and destroyed by the conjugated lytic peptide Phor21-FSHβ33–53 (Phor21-FSHβ). FSHR expression was not detected in the tumor vessel endothelial cells, which needs further re-evaluation.
[GRAPHICAL ABSTRACT] Schematic overview of the Phor21-FSHb33-53C/S (Phor21-FSHβ) conjugate or CTX specifically targeted to kill FSHR-positive cancer cells. (Figure created using BioRender.com). Phor21-FSHb33-53C/S conjugate, Phor21 lytic backbone conjugated with a native or modified fragment of the FSHb subunit (FSHb33-53); CTX, GnRH antagonist cetrorelix [Image: see text]
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s10020-025-01292-5.
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🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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