Skip to Content
Merck
  • Tumor-associated vacuolar ATPase subunit promotes tumorigenic characteristics in macrophages.

Tumor-associated vacuolar ATPase subunit promotes tumorigenic characteristics in macrophages.

Oncogene (2013-12-24)
G K Katara, M K Jaiswal, A Kulshrestha, B Kolli, A Gilman-Sachs, K D Beaman
ABSTRACT

Macrophage polarization contributes to distinct human pathologies. In tumors, a polarized M2 phenotype called tumor-associated macrophages (TAMs) are associated with promotion of invasion and angiogenesis. In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma/vesicular membranes and critically influences the metastatic behavior. In addition, the soluble, cleaved N-terminal domain of a2 isoform of V-ATPase (a2NTD) is associated with in vitro induction of pro-tumorigenic properties in monocytes. This activity of a2 isoform of V-ATPase (a2V) caused us to investigate its role in cancer progression through the evaluation of the immunomodulatory properties of a2NTD. Here, we present direct evidence that surface expression of V-ATPase is associated with macrophage polarization in tumor tissue. Macrophages from BALB/c mice (peritoneal/bone marrow derived) were stimulated with recombinant a2NTD in both ex vivo and in vivo systems and evaluated for TAM characteristics. a2V was highly expressed in tumor tissues (breast and skin) as well as on the surface of tumor cell lines. The a2NTD-stimulated macrophages (a2MΦ) acquired TAM phenotype, which was characterized by elevated expression of mannose receptor-1, Arginase-1, interleukin-10 and transforming growth factor-β. a2MΦ also exhibited increased production of other tumorigenic factors including matrix metalloproteinase-9 and vascular endothelial growth factor. Further, a2MΦ were cocultured with mouse B-16F0 melanoma cells for their functional characterization. The coculture of these a2MΦ subsequently increased the invasion and angiogenesis of less invasive B-16F0 cells. When cocultured with naive T cells, a2MΦ significantly inhibited T-cell activation. The present data establish the role of V-ATPase in modulating a macrophage phenotype towards TAMs through the action of a2NTD, suggesting it to be a potential therapeutic target in cancer.

MATERIALS
Product Number
Brand
Product Description

Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90% ((Assay))
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, Vetec, reagent grade, ≥98%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 10% in H2O
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 20% in H2O
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Supelco
L-Glutamine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
L-Glutamine, Vetec, reagent grade, ≥99%
SKU
Pack Size
Availability
Price
Quantity
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
SKU
Pack Size
Availability
Price
Quantity
Sodium laurilsulfate, European Pharmacopoeia (EP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity