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Marta M Kilian, Karin U Loeffler, Hans E Grossniklaus, Frank G Holz, Christiane Pfarrer, Christian Kurts, Martina C Herwig; The effects of macrophages on tumor growth characteristics in a mouse-model of intraocular melanoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5070.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the influence of tumor associated macrophages and age dependency on clinicopathological factors of intraocular melanoma using a murine ocular tumor model
Groups of 8-12 either untreated or systemically macrophage depleted CX3 CR1 GFP knock-in mice were examined at two different ages (young 8-10 weeks, old >10 months), respectively. After intravitreal injection of 1 x 105 HCmel12 melanoma cells, enucleation was performed at day 9. In histology (HE, PAS without hematoxylin), maximum intraocular tumor area was determined as well as co-option of retinal vessels, intratumoral endothelial lined vasculature and vasculogenic mimicry including its prognostic significant microcirculatory patterns. Microvasculature (VE Cadherin-Ab) and macrophage infiltration (GFP-Ab) in untreated mice were assessed by immunohistochemistry.
Over all groups, intratumoral endothelial-lined vasculature, vasculogenic mimicry and presence of microcirculatory patterns were not correlated with tumor size. Untreated old mice showed significantly more microcirculatory patterns compared with their younger counterparts. Macrophage depleted old mice exhibited significantly less patterns than untreated old mice. Compared to untreated mice of both age groups all macrophage depleted mice exhibited significant less patterns. Macrophage infiltration appeared to be more numerous in old than in the young mice.
The findings in this mouse-model indicate that tumor associated macrophages seem to have impact particularly on the formation of microcirculatory patterns. In untreated old mice microcirculatory patterns were distinctive in contrast to macrophage depleted mice. Tumor associated macrophages may have influence on the presence of these patterns, which in humans are known to be correlated with metastasis and therefor with worse prognosis.
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