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A macrophage autonomous Î±4Î²1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

ABSTRACT: Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, Î±4Î²1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. SmoA1 Tg MB tumor cells were sorted into CD15+ and CD15- populations. RNA from these samples were hybridized to Affymetrix Mouse Genome 1.0 ST array.

ORGANISM(S): Mus musculus

SUBMITTER: Lei Bao

PROVIDER: E-GEOD-41717 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A macrophage autonomous alpha4beta1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, M-NM-14M-NM-21 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. Bone marrow derived macrophages from five wild type and five Rac2 -/- mutant C57BL mice.

2012-10-02 | E-GEOD-41236 | biostudies-arrayexpress

A macrophage autonomous alpha4beta1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis.

2012-10-02 | GSE41236 | GEO

A macrophage autonomous α4β1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis.

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Epidermal growth factor shedding directs macrophage education in cancer

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2024-08-10 | PXD051695 | Pride

Scavenger Receptor A1 Prevents Non-Small Cell Lung Cancer Metastasis by Suppressing Macrophage Serum Amyloid A1 Expression

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A conserved atypical MFS family member orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion

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2019-04-01 | PXD011045 | Pride

Extracellular matrix educates a tumor macrophage phenotype found in ovarian cancer metastasis

Project description:Recent studies have shown the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and immunotherapy response. A question that remains is whether the ECM is directly educating the immune phenotypes seen in cancer. We identified a tumor-associated macrophage (TAM) population correlated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether ECM was capable of generating the TAM phenotype seen, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissues. ECM educated macrophages have a tissue remodeling and immunoregulatory phenotype, inducing altered T cell function. We conclude that the tumor ECM is directly educating this macrophage population found in cancer tissues. Therefore, current and emerging cancer therapies that target the tumor ECM may be tailored to improve macrophage phenotype and their downstream regulation of immunity.

2023-04-11 | PXD036940 | Pride

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