Arginine metabolic pathways involved in the modulation of tumor-induced angiogenesis by macrophages
Lilia Elena Davel1, María Adela Jasnis, Eulalia de la Torre
1Instituto de Oncología Angel H. Roffo, Av. San Martín 5481, CP 1417, Buenos Aires, Argentina.
Abstract:
Neovascularization, an essential step for tumor progression and metastasis development, can be modulated by the presence of macrophages (Mps) in the tumor microenvironment. The ability of Mps to regulate the angiogenicity of the LMM3 tumor cell line was studied. Peritoneal Mps from LMM3 tumor-bearing mice (TMps) potentiate in vivo LMM3 angiogenicity. These results were confirmed by CD31 immunoblotting assays. The activity of TMps depended on nitric oxide synthase (NOS) and arginase (A) activity. By immunoblotting we evidenced that AI and AII isoforms were up-regulated in TMps while the inducible and neuronal NOS isoforms were highly expressed in normal Mps. TMps might positively modulate tumor growth by stimulating angiogenic cascade mainly through polyamine synthesis.
Insights
Tumor-associated macrophages (TAMs) enhance tumor growth and blood vessel formation (angiogenesis) by modulating LMM3 tumor cells. This process involves specific enzyme activities and polyamine synthesis, highlighting TAMs as a therapeutic target.
Area of Science:
- Immunology
- Oncology
- Cancer Biology
Background:
- Neovascularization is crucial for tumor progression and metastasis.
- Macrophages (Mps) in the tumor microenvironment can modulate angiogenesis.
- The LMM3 tumor cell line's angiogenicity is influenced by Mps.
Purpose of the Study:
- To investigate how Mps regulate the angiogenicity of the LMM3 tumor cell line.
- To determine the mechanisms by which tumor-associated Mps (TMps) influence LMM3 tumor growth.
Main Methods:
- In vivo studies using LMM3 tumor-bearing mice.
- Peritoneal Mps from tumor-bearing mice (TMps) were isolated.
- CD31 immunoblotting assays were performed.
- Analysis of nitric oxide synthase (NOS) and arginase (A) activity and expression.
Main Results:
- TMps from LMM3 tumor-bearing mice potentiated in vivo LMM3 angiogenicity.
- TMp activity was dependent on nitric oxide synthase (NOS) and arginase (A) activity.
- AI and AII arginase isoforms were upregulated in TMps, while inducible and neuronal NOS isoforms were highly expressed in normal Mps.
Conclusions:
- TMps positively modulate tumor growth by stimulating the angiogenic cascade.
- Polyamine synthesis is a key pathway through which TMps promote angiogenesis.
- Targeting TAMs and their enzymatic activities may offer therapeutic strategies for cancer treatment.
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