Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers.
Exp Cell Res
; 406(1): 112734, 2021 09 01.
Article
en En
| MEDLINE
| ID: mdl-34265288
Chemotherapy is the preferred clinical treatment for advanced stage gastric cancer (GC) patients, of which efficacy could be markedly impaired due to the development of chemoresistance. Alternatively activated or M2-type tumor associated macrophages (TAMs) are recruited under chemotherapy and are highly implicated in the chemoresistance development, but underlying molecular mechanism for TAM activation is largely unknown. Here, we present that tumor-derived Leukemia inhibitory factor (LIF) induced by chemo drugs represses the chemo sensitivity of gastric tumor cells in a TAM-dependent manner. Mechanistically, cisplatin-induced HIF1α signaling activation directly drive the transcription of LIF, which promotes the resistance of gastric tumors to chemo drug. Further study revealed that tumor cell-derived LIF stimulates macrophages into tumor-supporting M2-type phenotype via activating STAT3 signaling pathway. Therapeutically, blocking LIF efficiently elevates chemo sensitivity of tumor cells and further represses the growth rates of tumors under chemotherapy. Therefore, our study reveals a novel insight in understanding the cross talking between tumor cells and immune cells and provides new therapeutic targets for gastric cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Cisplatino
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Resistencia a Antineoplásicos
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Factor Inhibidor de Leucemia
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Macrófagos Asociados a Tumores
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Exp Cell Res
Año:
2021
Tipo del documento:
Article