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Macrophage polarization by MSC-derived CXCL12 determines tumor growth.
Babazadeh, Shabnam; Nassiri, Seyed Mahdi; Siavashi, Vahid; Sahlabadi, Mohadeseh; Hajinasrollah, Mostafa; Zamani-Ahmadmahmudi, Mohamad.
Afiliação
  • Babazadeh S; Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  • Nassiri SM; Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. nasirim@ut.ac.ir.
  • Siavashi V; Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  • Sahlabadi M; Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  • Hajinasrollah M; Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • Zamani-Ahmadmahmudi M; Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
Cell Mol Biol Lett ; 26(1): 30, 2021 Jun 26.
Article em En | MEDLINE | ID: mdl-34174813
ABSTRACT

BACKGROUND:

Phenotypic and functional heterogeneity of macrophages is known to be the main reason for their ability to regulate inflammation and promote tumorigenesis. Mesenchymal stem cells (MSCs) are one of the principal cells commonly found in the tumor stromal niche, with capability of macrophage phenotypic switching. The objective of this study was to evaluate the role of C-X-C motif chemokine ligand 12 (CXCL12) produced by marrow-derived MSCs in the phenotypic and functional pattern of bone marrow-derived macrophages (BMDMs).

METHODS:

First, the CRISPR/Cas9 system was used for the CXCL12 gene knock-out in MSCs. Then, coculture systems were used to investigate the role of MSCsCXCL12-/- and MSCsCXCL12+/+ in determination of macrophage phenotype. To further analyze the role of the MSC-derived CXCL12 niche, cocultures of 4T1 mammary tumor cells and macrophages primed with MSCsCXCL12-/- or MSCsCXCL12+/+ as well as in-vivo limiting dilution assays were performed.

RESULTS:

Our results revealed that the expression of IL-4, IL-10, TGF-ß and CD206 as M2 markers was significantly increased in macrophages co-cultured with MSCsCXCL12+/+ , whereas the expression of IL-6, TNF-α and iNOS was conversely decreased. The number and size of multicellular tumor spheroids were remarkably higher when 4T1 cells were cocultured with MSCCXCL12+/+-induced M2 macrophages. We also found that the occurrence of tumors was significantly higher in coinjection of 4T1 cells with MSCCXCL12+/+-primed macrophages. Tumor initiating cells were significantly decreased after coinjection of 4T1 cells with macrophages pretreated with MSCsCXCL12-/-.

CONCLUSIONS:

In conclusion, our findings shed new light on the role of MSC-derived CXCL12 in macrophage phenotypic switching to M2, affecting their function in tumorigenesis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quimiocina CXCL12 / Células-Tronco Mesenquimais / Ativação de Macrófagos / Macrófagos / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quimiocina CXCL12 / Células-Tronco Mesenquimais / Ativação de Macrófagos / Macrófagos / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article