Evidence map›Paper›PMID 40490708›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Targeted destruction of follicle stimulating hormone receptor-positive cancer cells in vitro and in vivo by a lytic peptide Phor21-FSHβ conjugate.

Nafis A Rahman, Marcin Chrusciel, Donata Ponikwicka-Tyszko, Kamila Pulawska-Moon, Milena Doroszko, Joanna Stelmaszewska, Oliver J Keuzer, Adolfo Rivero-Muller, Piotr Bernaczyk, Grzegorz Zalewski and 6 more

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Nafis A RahmanInstitute of Biomedicine, University of Turku, Turku, Finland. nafis.rahman@utu.fi.
Marcin ChruscielInstitute of Biomedicine, University of Turku, Turku, Finland.
Donata Ponikwicka-TyszkoInstitute of Biomedicine, University of Turku, Turku, Finland.
Kamila Pulawska-MoonInstitute of Biomedicine, University of Turku, Turku, Finland.
Milena DoroszkoInstitute of Biomedicine, University of Turku, Turku, Finland.
Joanna StelmaszewskaDepartment of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Oliver J KeuzerPeptides & Elephants GmbH, Potsdam, Germany.
Adolfo Rivero-MullerDepartment of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Piotr BernaczykDepartment of Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
Grzegorz ZalewskiDepartment of Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
Peilan GuoState Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
Jorma ToppariInstitute of Biomedicine, University of Turku, Turku, Finland.
Xiangdong LiDepartment of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.
Adam J ZiecikDepartment of Hormonal Action Mechanisms, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Slawomir WolczynskiDepartment of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.
Ilpo HuhtaniemiInstitute of Biomedicine, University of Turku, Turku, Finland.

Funding

Magnus Ehrnroothin Säätiö no IDResearch Council of Finland no IDSigrid Juselius Foundation no IDTurun Yliopistollisen Keskussairaalan Koulutus- ja Tutkimussäätiö no IDUniwersytet Medyczny w Bialymstoku SUB/1/DN/20/002/1104
6 · The paper itself

Abstract

backgroundExtragonadal follicle-stimulating hormone (FSH) receptor (FSHR) expression in various cancers and their endothelial vessel cells has highlighted novel opportunities for targeted FSHR therapy.

methodsWe 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 in vivo. 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.

resultsPhor21 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 Fshr transcripts in the endothelium of these tumor vessel cells.

conclusionThis 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.

Indexed as

Antineoplastic AgentsFollicle Stimulating Hormone, beta SubunitNeoplasmsPeptidesReceptors, FSHAnimalsCell Line, TumorGonadotropin-Releasing HormoneHumansMaleMiceXenograft Model Antitumor AssaysAntineoplastic AgentsFollicle Stimulating Hormone, beta SubunitGonadotropin-Releasing HormonePeptidesReceptors, FSHCancerFSHRFSHβLytic peptidePhor21

Identifiers

PMID40490708
PMCPMC12147355

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.