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Investigating Chemokine-Matrix Networks in Breast Cancer: Tenascin-C Sets the Tone for CCL2

Gschwandtner, Martha ; Gammage, Anís N ; Deligne, Claire ; Mies, Linda F M ; Domaingo, Alissa ; Murdamoothoo, Devardarssen ; Loustau, Thomas ; Schwenzer, Anja ; Derler, Rupert ; Carapito, Raphael ; Koch, Manuel ; Mörgelin, Matthias ; Orend, Gertraud ; Kungl, Andreas J ; Midwood, Kim S

International journal of molecular sciences, 2023-05, Vol.24 (9), p.8365 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Investigating Chemokine-Matrix Networks in Breast Cancer: Tenascin-C Sets the Tone for CCL2
Autor: Gschwandtner, Martha ; Gammage, Anís N ; Deligne, Claire ; Mies, Linda F M ; Domaingo, Alissa ; Murdamoothoo, Devardarssen ; Loustau, Thomas ; Schwenzer, Anja ; Derler, Rupert ; Carapito, Raphael ; Koch, Manuel ; Mörgelin, Matthias ; Orend, Gertraud ; Kungl, Andreas J ; Midwood, Kim S
Assuntos: Analysis ; Animals ; B cells ; Binding ; Biochemistry, Molecular Biology ; Breast cancer ; CCL2 ; Cell activation ; Cell culture ; Cell survival ; Cells ; Chemokine CCL2 - metabolism ; Chemokines ; Chemokines - metabolism ; Development and progression ; ErbB-2 protein ; extracellular matrix ; Extracellular Matrix - metabolism ; Fibroblasts ; Growth factors ; Immune response ; Life Sciences ; Liu, Timothy ; Macrophages ; Macrophages - metabolism ; MCP-1 ; Medical prognosis ; Metastasis ; Mice ; Monocyte chemoattractant protein 1 ; Myeloid cells ; Neoplasms - metabolism ; Phenotypes ; Proteins ; Scientific equipment and supplies industry ; Signal Transduction ; Survival ; Tenascin ; Tenascin - metabolism ; Tenascin C ; Tumor microenvironment ; Tumorigenesis ; Tumors
É parte de: International journal of molecular sciences, 2023-05, Vol.24 (9), p.8365
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Bidirectional dialogue between cellular and non-cellular components of the tumor microenvironment (TME) drives cancer survival. In the extracellular space, combinations of matrix molecules and soluble mediators provide external cues that dictate the behavior of TME resident cells. Often studied in isolation, integrated cues from complex tissue microenvironments likely function more cohesively. Here, we study the interplay between the matrix molecule tenascin-C (TNC) and chemokine CCL2, both elevated in and associated with the progression of breast cancer and playing key roles in myeloid immune responses. We uncover a correlation between TNC/CCL2 tissue levels in HER2+ breast cancer and examine the physical and functional interactions of these molecules in a murine disease model with tunable TNC levels and in in vitro cellular and cell-free models. TNC supported sustained CCL2 synthesis, with chemokine binding to TNC via two distinct domains. TNC dominated the behavior of tumor-resident myeloid cells; CCL2 did not impact macrophage survival/activation whilst TNC facilitated an immune suppressive macrophage phenotype that was not dependent on or altered by CCL2 co-expression. Together, these data map new binding partners within the TME and demonstrate that whilst the matrix exerts transcriptional control over the chemokine, each plays a distinct role in subverting anti-tumoral immunity.
Editor: Switzerland: MDPI AG
Idioma: Inglês;Francês

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Investigating Chemokine-Matrix Networks in Breast Cancer: Tenascin-C Sets the Tone for CCL2

Gschwandtner, Martha ; Gammage, Anís N ; Deligne, Claire ; Mies, Linda F M ; Domaingo, Alissa ; Murdamoothoo, Devardarssen ; Loustau, Thomas ; Schwenzer, Anja ; Derler, Rupert ; Carapito, Raphael ; Koch, Manuel ; Mörgelin, Matthias ; Orend, Gertraud ; Kungl, Andreas J ; Midwood, Kim S

Switzerland: MDPI AG

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