Evidence that macrophages transfer arachidonic acid and cholesterol to tissues <i>in vivo</i>

Peres, Cleto Kaveski; Bittencourt, Paulo Ivo Homem de; Mendonça, J. R.; Curi, Rui

doi:10.1002/cbf.1029

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…Recently, thyroid carcinoma-and neuroblastoma-induced macrophages were found to upregulate lipid biosynthesis in vitro, supporting their pro-tumoral function including cytokine production [106]. Combined with the finding that macrophages can secrete lipids in vitro and in vivo [107,108], and TAM-derived extracellular vesicles containing lipids [89] this may indicate that not only CAFs and adipocytes but also TAMs "feed" cancer cells. Additionally, Arg1-mediated polyamine production by macrophages increases breast cancer cell proliferation in vitro [109].…”

Section: Effect Of Tam Metabolism On Tumor Progressionmentioning

confidence: 90%

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Goede

Driessen

Bossche

2020

Biology

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Tumors consist of a wide variety of cells, including immune cells, that affect tumor progression. Macrophages are abundant innate immune cells in the tumor microenvironment (TME) and are crucial in regulating tumorigenicity. Specific metabolic conditions in the TME can alter the phenotype of tumor-associated macrophages (TAMs) in a direction that supports their pro-tumor functions. One of these conditions is the accumulation of metabolites, also known as oncometabolites. Interactions of oncometabolites with TAMs can promote a pro-tumorigenic phenotype, thereby sustaining cancer cell growth and decreasing the chance of eradication. This review focuses on the metabolic cancer-macrophage crosstalk in the TME. We discuss how cancer cell metabolism and oncometabolites affect macrophage phenotype and function, and conversely how macrophage metabolism can impact tumor progression. Lastly, we propose tumor-secreted exosome-mediated metabolic signaling as a potential factor in tumorigenesis. Insight in these processes may contribute to the development of novel cancer therapies.

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Section: Effect Of Tam Metabolism On Tumor Progressionmentioning

confidence: 90%

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Goede

Driessen

Bossche

2020

Biology

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“… 41–43 Furthermore, it has been shown that labeled lipid loaded-macrophages injected into the blood stream in vivo transfer labeled cholesterol and arachidonic acid to tissues in rats. 44 This property of macrophages to transfer lipids may, in the context of tumor-induced macrophages, contribute to their protumoral function by feeding tumor cells with lipids for membrane formation and proliferation, and future studies are warranted to assess this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

Rabold¹,

Aschenbrenner²,

Thiele

et al. 2020

J Immunother Cancer

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BackgroundTumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs.MethodsIn a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways.ResultsBased on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME.ConclusionsTaken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME.

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“…[ 14 C]-Labeled CHOL and AA can be transferred from resident-and TG-Mφ to various tissues and organs in rats (31). The physiological role of this lipid transfer on modulation of acceptor cell function (e.g., LY proliferation and cytokine production) in vivo still has to be determined.…”

Section: Discussionmentioning

confidence: 99%

Transfer of arachidonic acid from lymphocytes to macrophages

Peres

Sampaio

Cury

et al. 2003

Lipids

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The incorporation and oxidation of arachidonic acid (AA) by rat lymphocytes (LY), the transfer of AA from LY to rat macrophages (Mphi) in co-culture, and the subsequent functional impact on Mphi phagocytosis were investigated. The rate of incorporation of [1-14C]AA by untreated-LY and TG (thioglycolate treated)-LY (TG-LY) was 158 +/- 8 nmol/10(10) LY per h for both untreated-LY and TG-LY. The oxidation of AA was 3.4-fold higher in TG-LY as compared with untreated cells. LY from TG-injected rats had a 2.5-fold increase in the oxidation of palmitic (PA), oleic (OA), and linoleic (LA) acids. After 6 h of incubation, [14C] from AA was distributed mainly into phospholipids. The rate of incorporation into total lipids was 1071 nmol/10(10) cells in untreated-LY and 636 nmol/10(10) cells in TG-LY. [14C]AA was transferred from LY to co-cultured Mphi in substantial amounts (8.7 nmol for untreated and 15 nmol per 10(10) for TG cells). Exogenously added AA, PA, OA, and LA caused a significant reduction of phagocytosis by resident cells. Mphi co-cultured with AA-preloaded LY showed a significant reduction of the phagocytic capacity (about 40% at 35 microM). LY preloaded with PA, LA, and OA also induced a reduction in phagocytic capacity of co-cultured Mphi. TG treatment abolished the AA-induced inhibition of phagocytosis in Mphi co-cultured with TG-LY. Therefore, the transfer of AA between leukocytes is a modulated process and may play an important role in controlling inflammatory and immune response.

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Evidence that macrophages transfer arachidonic acid and cholesterol to tissues in vivo

Cited by 8 publications

References 19 publications

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

Transfer of arachidonic acid from lymphocytes to macrophages

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