Distribution of macrophage polarization markers in human atherosclerosis

Stöger, J. Lauran; Gijbels, Marion J.J.; Velden, Saskia van der; Manca, Marco; Loos, Chris M. van der; Biessen, Erik A. L.; Daemen, Mat J.A.P.; Lutgens, Esther; Winther, Menno P.J. de

doi:10.1016/j.atherosclerosis.2012.09.013

Cited by 514 publications

(457 citation statements)

References 39 publications

Supporting

Mentioning

400

Contrasting

Unclassified

Order By: Relevance

“…52 However, MARCO does not exclusively exist on M2 macrophages being associated with M1 and dendritic cell activation. [53][54][55] Increased CXCL12 promotes neo-angiogenesis, and supported by increased expression of SRPX2, may also mediate angiogenesis providing further evidence that tumorassociated macrophages in telomerase with macrophages are more tumor-promoting compared with those in alternative lengthening of telomeres with macrophages. 56,57 Telomerase with macrophage tumors were associated with a reduced extent of surgical resection, suggesting tumor-associated macrophages in telomerase with macrophages are more infiltrative and thus damaging.…”

Section: Discussionmentioning

confidence: 87%

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

et al. 2016

View full text Add to dashboard Cite

Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumorassociated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P = 0.0004, and telomerase with and without macrophages P = 0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs 476% for all other subtypes, P = 0.014). In summary, different immune signatures are found among telomere maintenance mechanism-based subgroups in glioblastoma. The reduced extent of surgical resection of telomerase-positive tumors with macrophages suggests that some tumor-associated macrophages are more unfavorable.

show abstract

Section: Discussionmentioning

confidence: 87%

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…55 To clearly determine the relevance of CCL2 expression and macrophage recruitment and activity in triple-negative breast cancer, it would be necessary to perform immunostaining for markers identifying these macrophage subtypes, including M1-and M2-like cells, and compare their expression patterns with a panmacrophage marker. [55][56][57] These studies are beyond the scope of this manuscript but are of interest in the future. In summary, our studies demonstrate an association between poor outcome in basal-like breast cancer and CCL2 expression in the stroma.…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Yao

Staggs

et al. 2016

Modern Pathology

View full text Add to dashboard Cite

Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n = 427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR = 7.51 P = 0.007) was associated with a greater hazard than cancer stage (HR = 2.45, P = 0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.

show abstract

“…Galectin-3 (Gal-3) is secreted by macrophages; promotes eosinophil, neutrophil, and monocyte adhesion and recruitment, thereby enhancing inflammation [24]; and is a known marker of heart failure prognosis [25]. Gal-3 binding protein (Gal-3BP) is a soluble marker of M1-polarized macrophages [26], which are thought to be associated with inflamed, vulnerable plaques [27]; serum Gal-3BP levels have been found to be elevated in individuals with cancer or HIV infection [28,29].…”

mentioning

confidence: 99%

Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men

Hanna

Lin

Post

et al. 2017

The Journal of Infectious Diseases

View full text Add to dashboard Cite

(See the editorial commentary by Feinstein and Lloyd-Jones on pages 1343-5.)Background. Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.Methods. We examined 778 women (74% HIV + ) in the Women's Interagency HIV Study and 503 men (65% HIV + ) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years.Results. Marker levels were higher in HIV + persons versus HIV -persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV + men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque.Conclusions. sCD14 and sCD163 may play important roles in atherogenesis among HIV + persons.

show abstract

Distribution of macrophage polarization markers in human atherosclerosis

Cited by 514 publications

References 39 publications

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men

Contact Info

Product

Resources

About