Tumor Versus Tumor-Associated Macrophages: How Hot is the Link?

Guruvayoorappan, Chandrasekharan

doi:10.1177/1534735408319060

Cited by 66 publications

(60 citation statements)

References 79 publications

(84 reference statements)

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“…TAMs secreted a wide range of pro-angiogenic mediators such as bFGF, thymidine phosphorylase, uPA, and adrenomedullin [1]. At hypoxic tumor sites, HIF-1α up-regulates VEGF-A expression in TAMs [9] and, MMP-1, -7 and -9 proteolytic enzymes [10–12]. CXCL12 expression in gastric cancer and activation of the β-catenin pathway correlate with increased microvascular density and invasiveness [13, 14].…”

Section: Introductionmentioning

confidence: 99%

PEDF increases the tumoricidal activity of macrophages towards prostate cancer cells in vitro

et al. 2017

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BackgroundAlthough inflammation and prostate cancer (PCa) have been linked, the molecular interactions between macrophages and PCa cells are poorly explored. Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor factor. We previously showed that PEDF induces macrophages recruitment in vitro, correlates with macrophages density in human prostate, and stimulates macrophages polarization towards the classically activated pathway. Here, we demonstrate that PEDF modulates the interaction between macrophages and PCa cells through a bidirectional signalling leading to tumor cell apoptosis and phagocytosis.MethodsRAW 264.7 and THP-1 cells, and BMDMs were grown in vitro as mono- or co-cultures with PC3 or CL1 tumor cells. The effects of PEDF and its derived P18 peptide were measured on macrophages differentiation, migration, and superoxide production, and tumor cell apoptosis and phagocytosis. PEDF receptors (ATP5B, PNPLA2, and LRP6) and CD47 mRNA and protein expression were quantified in macrophages and tumor cells by quantitative RT-PCR, western blot, immunofluorescence and flow cytometry.ResultsWe found that PEDF induced the migration of macrophages towards tumor 3D spheroids and 2D cultures. In co-culture, PEDF increased PCa cells phagocytosis through an indirect apoptosis-dependent mechanism. Moreover, PEDF stimulated the production of superoxide by macrophages. Conditioned media from macrophages exposed to PEDF induced tumor cells apoptosis in contrast to control conditioned media suggesting that ROS may be involved in tumor cells apoptosis. ATP5B and PNPLA2 PEDF receptors on macrophages and CD47 on tumor cells were respectively up- and down-regulated by PEDF. As PEDF, blocking CD47 induced phagocytosis. Inhibiting ATP5B reduced phagocytosis. Inversely, PNPLA2 inhibition blocks differentiation but maintains phagocytosis. CD47-induced phagocytosis was partially reverted by ATP5B inhibition suggesting a complementary action. Similar effects were observed with P18 PEDF-derived peptide.ConclusionsThese data established that modulating the molecular interactions between macrophages and PCa cells using PEDF may be a promising strategy for PCa treatment.

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Section: Introductionmentioning

confidence: 99%

PEDF increases the tumoricidal activity of macrophages towards prostate cancer cells in vitro

et al. 2017

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“…This study concluded that localization of macrophages, regulated by Sema3A/Nrp-1 signaling, plays an important role in their functional states [51]. In addition to degrading the basement membranes and ECM, TAM provide activated endothelial cells with an environment (via increased availability of VEGF and production of CXLC-1, -2, and -8), in which they can migrate, proliferate, and form new blood vessels [52,53,54]. …”

Section: Tumor-associated Macrophagesmentioning

confidence: 99%

Nanomedicine Strategies to Target Tumor-Associated Macrophages

Binnemars-Postma

Storm

Prakash

2017

IJMS

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In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.

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“…In contrast to the reactive macrophages which are characterized by a so-called M1 phenotype, TAMs are alternatively activated and acquire an M2 phenotype, thus promoting tumor growth, angiogenesis, metastasis, as well as suppressing potential anti-tumor immune activities. TAMs affect vascular density and ECM by secreting a vast array of pro-angiogenetic factors and proteolytic enzymes including VEGF, FGF, PDGF, TNF-, MMPs, plasmin, urokinasetype plasminogen activator (uPA) and the uPA receptor (uPAR) (Guruvayoorappan, 2008;Allavena et al, 2008). One key role for the microenvironment that has gained prominent recognition is neoangiogenesis.…”

Section: Cells Of the Tumor Microenvironmentmentioning

confidence: 99%

“…TAMs enhance the invasive capacity of cancer cells (Lewis & Pollard, 2006). This effect may depend on the expression of MMPs and uPA and its receptor uPAR which enhances the motility and invasion of cancer cells (Guruvayoorappan, 2008). Neutrophils.…”

Section: Cells Of the Microenvironment Cancer Associated Fibroblasts mentioning

confidence: 99%