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  Paracrine Activin-A signaling promotes melanoma growth and metastasis through immune evasion

Donovan, P., Dubey, O., Kallioinen, S., Rogers, K., Muehlethaler, K., Müller, P., et al. (2017). Paracrine Activin-A signaling promotes melanoma growth and metastasis through immune evasion. The Journal of Investigative Dermatology: Official Journal of the Society for Investigative Dermatology and the European Society for Dermatological Research, 137(12), 2578-2587. doi:10.1016/j.jid.2017.07.845.

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Genre: Zeitschriftenartikel

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 Urheber:
Donovan, P, Autor
Dubey, OA, Autor
Kallioinen, S, Autor
Rogers, KW1, Autor           
Muehlethaler, K, Autor
Müller, P1, Autor           
Rimoldi, D, Autor
Constam, DB, Autor
Affiliations:
1Müller Group, Friedrich Miescher Laboratory, Max Planck Society, ou_3008690              

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Schlagwörter: -
 Zusammenfassung: The secreted growth factor Activin-A of the transforming growth factor β family and its receptors can promote or inhibit several cancer hallmarks including tumor cell proliferation and differentiation, vascularization, lymphangiogenesis and inflammation. However, a role in immune evasion and its relationship with tumor-induced muscle wasting and tumor vascularization, and the relative contributions of autocrine versus paracrine Activin signaling remain to be evaluated. To address this, we compared the effects of truncated soluble Activin receptor IIB as a ligand trap, or constitutively active mutant type IB receptor versus secreted Activin-A or the related ligand Nodal in mouse and human melanoma cell lines and tumor grafts. We found that although cell-autonomous receptor activation arrested tumor cell proliferation, Activin-A secretion stimulated melanoma cell dedifferentiation and tumor vascularization by functional blood vessels, and it increased primary and metastatic tumor burden and muscle wasting. Importantly, in mice with impaired adaptive immunity, the tumor-promoting effect of Activin-A was lost despite sustained vascularization and cachexia, suggesting that Activin-A promotes melanoma progression by inhibiting antitumor immunity. Paracrine Activin-A signaling emerges as a potential target for personalized therapies, both to reduce cachexia and to enhance the efficacy of immunotherapies.

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Sprache(n): eng - English
 Datum: 2017-12
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.jid.2017.07.845
PMID: 28844941
 Art des Abschluß: -

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Titel: The Journal of Investigative Dermatology : Official Journal of the Society for Investigative Dermatology and the European Society for Dermatological Research
  Andere : J. Invest. Dermatol.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: New York, NY [etc.] : Elsevier Science Pub. Co. [etc.]
Seiten: - Band / Heft: 137 (12) Artikelnummer: - Start- / Endseite: 2578 - 2587 Identifikator: ISSN: 0022-202X
CoNE: https://pure.mpg.de/cone/journals/resource/954925414921_3