Location, Location, Location: Macrophage Positioning within Tumors Determines Pro- or Antitumor Activity

Rivera, Lee B.; Bergers, Gabriele

doi:10.1016/j.ccr.2013.11.014

Cited by 43 publications

(35 citation statements)

References 10 publications

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“…8 Moreover, our data clearly demonstrate that macrophages can exert tumor-promoting activities, such as inducing EMT in the pancreatic ductal epithelium, by exerting pro-inflammatory properties of similar magnitude, or even stronger than, their pronounced antiinflammatory phenotype, substantiating the view that distinct modes of inflammation contribute to tumor initiation and progression (Fig. 1).…”

supporting

confidence: 57%

M1 and M2: there is no “good” and “bad”—How macrophages promote malignancy-associated features in tumorigenesis

Helm

Held‐Feindt²,

Schäfer

et al. 2014

OncoImmunology

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supporting

confidence: 57%

M1 and M2: there is no “good” and “bad”—How macrophages promote malignancy-associated features in tumorigenesis

Helm

Held‐Feindt²,

Schäfer

et al. 2014

OncoImmunology

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“…This study also demonstrated that Sema3A and its receptors mediate the migration through activation of vascular endothelial growth factor receptor (VEGFR). Similar results even suggested that Sema3A/NRP-1 signaling was involved in the macrophage reprogramming [64]. Expression of Sema3A and its receptors have been identified on monocyte-derived macrophages [65].…”

Section: Macrophage and Nerve Interaction In Endometriosismentioning

confidence: 67%

Macrophage and nerve interaction in endometriosis

Xie

Yao

et al. 2017

J Neuroinflammation

119

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Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis. Upon secretion of multiple abnormal signal molecules by the endometriotic lesion, macrophages could alter their location and phenotype. These changes facilitate the accommodation of the aberrant microenvironment and the exacerbation of disease progression. Second, the infiltration of nerve fibers and their abnormal distribution are proved to be involved in the generation of endometriosis-associated pain and inflammatory response. An imbalance in sensory and sympathetic innervation and the abnormal secretion of different cytokines could mediate neurogenesis and subsequent peripheral neuroinflammation in endometriosis. Although endometriosis creates an inflammatory milieu promoting macrophage infiltration and an imbalanced innervation, interaction between macrophages and nerve fibers in this process remains unknown. The aim of this review is to highlight the role of macrophage and nerve interaction in endometriosis, where macrophage recruitment and neurogenesis can be the underlying mechanism of neuroinflammation and pathogenesis of endometriosis.

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“…Localization of macrophages within tumors appears to be critically important for their function and activation state (39)(40)(41). In the MIP-2 overexpression model, reduced macrophage activation in Hpa-KO tumors (Fig.…”

Section: Discussionmentioning

confidence: 94%

Heparanase is required for activation and function of macrophages

Gutter-Kapon¹,

Alishekevitz²,

Shaked³

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

169

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The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, very little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here we used a genetic approach and examined the behavior and function of macrophages isolated from wild-type (WT) and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages express lower levels of cytokines (e.g., TNFα, IL1-β) and exhibit lower motility and phagocytic capacities. Intriguingly, inoculation of control monocytes together with Lewis lung carcinoma (LLC) cells into Hpa-KO mice resulted in nearly complete inhibition of tumor growth. In striking contrast, inoculating LLC cells together with monocytes isolated from Hpa-KO mice did not affect tumor growth, indicating that heparanase is critically required for activation and function of macrophages. Mechanistically, we describe a linear cascade by which heparanase activates Erk, p38, and JNK signaling in macrophages, leading to increased c-Fos levels and induction of cytokine expression in a manner that apparently does not require heparanase enzymatic activity. These results identify heparanase as a key mediator of macrophage activation and function in tumorigenesis and cross-talk with the tumor microenvironment.

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Location, Location, Location: Macrophage Positioning within Tumors Determines Pro- or Antitumor Activity

Cited by 43 publications

References 10 publications

M1 and M2: there is no “good” and “bad”—How macrophages promote malignancy-associated features in tumorigenesis

M1 and M2: there is no “good” and “bad”—How macrophages promote malignancy-associated features in tumorigenesis

Macrophage and nerve interaction in endometriosis

Heparanase is required for activation and function of macrophages

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