Alveolar Macrophage Polarisation in Lung Cancer

Almatroodi, Saleh A.; McDonald, Christine F; Pouniotis, Dodie

doi:10.1155/2014/721087

Cited by 31 publications

(34 citation statements)

References 64 publications

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“…In tumor environments, macrophages polarize toward an alternatively activated or M2 phenotype that promotes tumorigenesis via a variety of mechanisms (14). If administration of SOCS3 liposomes is ever to be considered for in vivo prevention/treatment of lung cancer or other tumors, it is important to ensure that SOCS3 liposomes do not augment the protumor effects of AMs.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we uncovered a potentially novel role for AMs in restraining inflammatory responses in the lung via the constitutive secretion of SOCS3 within extracellular vesicles (EVs); these EVs are internalized by respiratory ECs, wherein they inhibit STAT activation in response to cytokines, such as IL-6 (11,12). While resident AM functions such as phagocytosis and cytokine secretion are altered in lung cancer patients (13), existing data on the role of the resident AM in lung cancer development and progression are limited and contradictory (14). Here, we identify a potential of AMs to provide exogenous SOCS3 secreted in EVs to ECs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alveolar macrophage secretion of vesicular SOCS3 represents a platform for lung cancer therapeutics

Speth¹,

Penke²,

Bazzill³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alveolar macrophage secretion of vesicular SOCS3 represents a platform for lung cancer therapeutics

Speth¹,

Penke²,

Bazzill³

et al. 2019

JCI Insight

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“…Alveolar macrophages (AMs) are likely to be of central importance in the lung cancer immune response. A dual role of macrophages in lung cancer was suggested with the idea that AMs may both inhibit and/or promote tumor progression [40]. There are two different types of macrophages, including classical M1 and alternative M2 macrophages, which respectively exhibit antitumor and protumor effects.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte Cell-Derived Chemotaxin 2 Retards Non-Small Cell Lung Cancer Progression Through Antagonizing MET and EGFR Activities

Hung¹,

Chang²,

Cheng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy is a clinical option for non-small cell lung cancer (NSCLC) harboring activating EGFR mutations or for cancer with wild-type (WT) EGFR when chemotherapy has failed. MET receptor activation or MET gene amplification was reported to be a major mechanism of acquired resistance to EGFR-TKI therapy in NSCLC cells. Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that was shown to suppress metastasis of hepatocellular carcinoma via inhibiting MET activity. Until now, the biological function responsible for LECT2’s action in human NSCLC remains unclear. Methods: LECT2-knockout (KO) mice and NOD/SCID/IL2rgnull (NSG) mice were respectively used to investigate the effects of LECT2 on the tumorigenicity and metastasis of murine (Lewis lung carcinoma, LLC) and human (HCC827) lung cancer cells. The effect of LECT2 on in vitro cell proliferation was evaluated, using MTS and colony formation assays. The effect of LECT2 on cell motility was evaluated using transwell migration and invasion assays. An enzyme-linked immunosorbent assay was performed to detect secreted LECT2 in plasma and media. Co-immunoprecipitation and Western blot assays were used to investigate the underlying mechanisms of LECT2 in NSCLC cells. Results: Compared to WT mice, mice with LECT2 deletion exhibited enhanced growth and metastasis of LLC cells, and survival times decreased in LLC-implanted mice. Overexpression of LECT2 in orthotopic human HCC827 xenografts in NSG mice resulted in significant inhibition of tumor growth and metastasis. In vitro, overexpression of LECT2 or treatment with a recombinant LECT2 protein impaired the colony-forming ability and motility of NSCLC cells (HCC827 and PC9) harboring high levels of activated EGFR and MET. Mechanistic investigations found that LECT2 bound to MET and EGFR to antagonize their activation and further suppress their common downstream pathways: phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase. Conclusion: EGFR-MET signaling is critical for aggressive behaviors of NSCLC and is recognized as a therapeutic target for NSCLC especially for patients with acquired resistance to EGFR-TKI therapy. Our findings demonstrate, for the first time, that LECT2 functions as a suppressor of the progression of NSCLC by targeting EGFR-MET signaling.

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“…While clearly implicated in inhibiting tumor growth with consequent tumor regression, macrophages have also been demonstrated to have pro-tumor functions resulting in tumor progression. Moreover, a number of cytokines have been described as possessing dual roles in NSCLC [ 19 ]. Further studies are needed to examine macrophage functions in NSCLC under different conditions and to relate this to patient response to treatment and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

et al. 2018

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BackgroundNon-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival.MethodsLung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually.ResultsPredominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05).ConclusionsThis study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients’ survival.Trial registrationClinicalTrials.gov NCT01955343, registered on September 27, 2013

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Alveolar Macrophage Polarisation in Lung Cancer

Cited by 31 publications

References 64 publications

Alveolar macrophage secretion of vesicular SOCS3 represents a platform for lung cancer therapeutics

Alveolar macrophage secretion of vesicular SOCS3 represents a platform for lung cancer therapeutics

Leukocyte Cell-Derived Chemotaxin 2 Retards Non-Small Cell Lung Cancer Progression Through Antagonizing MET and EGFR Activities

Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

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