Predominance of M2-polarized macrophages in bladder cancer affects angiogenesis, tumor grade and invasiveness

Takeuchi, Hisashi; Tanaka, Michio; Tanaka, Ayako; Tsunemi, Akisa; Yamamoto, Hirotaka

doi:10.3892/ol.2016.4392

Cited by 69 publications

(59 citation statements)

References 28 publications

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“…TAMs and their alternative activation together with cytokines and growth factors are trapped in tumor stroma and strongly contribute to the progression of OS [36]. Interestingly, in contrast to most other tumor types, M2 polarized macrophages reduce metastasis and improve survival in high-grade OS patients [25]. In vitro studies demonstrated that human macrophages can be stimulated by Mifamurtide to exert anti-tumor activity against OS cells [31].…”

Section: Discussionmentioning

confidence: 99%

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Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells

et al. 2020

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Tumor-associated macrophages and their alternative activation states together with cytokines and growth factors trapped in tumor microenvironment contribute to the progression of OS. In contrast to other tumor types, M2 polarized macrophages, reduce metastasis and improve survival in osteosarcoma patients. Mifamurtide is an immunomodulatory drug given together with standard adjuvant chemotherapy in high-grade osteosarcoma to improve outcome. Macrophages obtained from peripheral blood mononucleated cells of healthy donors and MG63 cells were cultured alone and together, and treated with Mifamurtide. We analyzed the effects of Mifamurtide on macrophage polarization and on MG63 proliferation, migration and differentiation, evaluating the expression of M1/M2 and osteoblast markers and molecules involved in metastasis and proliferation pathways. Our data suggest that Mifamurtide, switching macrophage polarization towards a TAM-like intermediate M1/M2 phenotype, may modulate the delicate balance between pro-inflammatory and immunomodulatory macrophage functions. Moreover, Mifamurtide may inhibit the cellular proliferation and induce the tumor cell differentiation, probably through the down regulation of pSTAT3, pAKT and IL-17R.

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Section: Discussionmentioning

confidence: 99%

“…In contrast to many other tumor types, M2 polarized macrophages, reduce metastasis and improve survival in high-grade OS patients. Macrophage polarization is also able to modulate iron sequestration and release [24][25][26][27][28].…”

Section: Research Papermentioning

confidence: 99%

Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells

et al. 2020

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“…Subsequent to adhesion to vascular endothelial cells, Mφ mature, begin phagocytosis, intracellular digestion, antigen presentation of Mφ and finally digest the crystal (24). However, M1 macrophages are pro-inflammatory, and M2 anti-inflammatory (25); M1s are associated with adipocytes and metabolic syndrome, whereas M2s are associated with organ restoration (26,27) and carcinogenesis (28). When crystals adhere to the renal tubular epithelium, M1-associated genes are highly expressed and promoted by adipocytes (29); in mice in which M2 macrophages are dysfunctional, M1 macrophages and kidney stone formation are increased (30).…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics in urolithiasis formation according to body mass index

Takeuchi

Aoyagi

2019

biom rep

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Although urolithiasis is considered to be strongly associated with lifestyle habits, there are numerous cases in which urolithiasis develops despite a non-obese body type or healthy lifestyle habits. However, in clinical practice, the diet therapy and lifestyle changes instructed for the prevention of recurrence of urolithiasis are almost identical in numerous cases. Therefore, the present study examined the effect of body mass index (BMI) on urolithiasis and its surrounding environment in patients, by analyzing the number of normal-and high-BMI (healthy and overweight) patients with urolithiasis. The present study analyzed 63 patients with urolithiasis for whom height and weight were measured at our hospital (Tokyo Medical University Ibaraki Medical Center). BMI <25 represents healthy body types and BMI ≥25 BMI defines overweight body types. Thus, patients were then grouped by BMI-defined body type using a threshold value of 25 accordingly. It was observed that a higher percentage of males were obese compared with females. Upon comparing the normaland high-BMI groups, no significant difference was observed in uric acid level, urine pH or calculus number between the two groups. Liver computed tomography (CT) values were significantly lower in the high-BMI group compared with the normal-BMI group. There was no significant correlation between calculus size counts and BMI. However, a significant negative correlation was observed between BMI and the liver CT value. These results suggest that liver CT values correlated negatively with BMI, but the data indicates that other mechanisms unassociated with a fatty liver may be involved in urolithiasis in non-obese patients. The results of the present study suggest that physicians should consider the mechanism involved in preventing the recurrence of urolithiasis.

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“…Takeuchi et al (2016) to correlate the prevalence of M2 macrophages, angiogenesis, and clinic-pathological features in bladder cancer showed higher density of M2 macrophages in invasive bladder cancer in relation to non-muscle invasive cancers. Moreover, the higher the distribution of microvessels, the greater the degree of severity of cancer, and the predominance of M2 macrophage correlated to the amount of microvessels in bladder cancer and can have prognostic value for this type of cancer [45]. …”

Section: Angiogenesis and Lymphangiogenesismentioning

confidence: 99%

“…Thus, it was proposed that the mTOR pathway could be a critical element in the regulation of TAMs differentiation [45]. …”

Section: Angiogenesis and Lymphangiogenesismentioning

confidence: 99%

The Fate of the Tumor in the Hands of Microenvironment: Role of TAMs and mTOR Pathway

Soave

Miguel

Tomé

et al. 2016

Mediators of Inflammation

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Since 2000, written with elegance and accuracy, Hanahan and Weinberg have proposed six major hallmarks of cancer and, together, they provide great advances to the understanding of tumoral biology. Our knowledge about tumor behavior has improved and the investigators have now recognized that inflammatory microenvironment may be a new feature for the tumor entities. Macrophages are considered as an important component of tumoral microenvironment. Biologically, two forms of activated macrophages can be observed: classically activated macrophages (M1) and alternative activated macrophages (M2). Despite the canonical pathways that control this puzzle of macrophages polarization, recently, mTOR signaling pathway has been implicated as an important piece in determining the metabolic and functional differentiation of M1 and M2 profiles. Currently, it is believed that macrophages related to tumoral microenvironment present an “M2-like” feature promoting an immunosuppressive microenvironment enhancing tumoral angiogenesis, growth, and metastasis. In the present review we discuss the role of macrophages in the tumor microenvironment and the role of mTOR pathway in M1 and M2 differentiation. We also discuss the recent findings in M1 and M2 polarization as a possible target in the cancer therapy.

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Predominance of M2-polarized macrophages in bladder cancer affects angiogenesis, tumor grade and invasiveness

Cited by 69 publications

References 28 publications

Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells

Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells

Clinical characteristics in urolithiasis formation according to body mass index

The Fate of the Tumor in the Hands of Microenvironment: Role of TAMs and mTOR Pathway

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