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Distribution of Mast Cells (MC), Toll‐Like Receptor 2 (TLR2) and Receptor for Advanced Glycation End Products (RAGE) May Reflect the Nature of Tumor Neovascularization in Human Medulloblastoma
Author(s) -
Szukiewicz Dariusz,
LaureKamionowska Milena,
Maslinska Danuta
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.3
Subject(s) - medulloblastoma , angiogenesis , immunohistochemistry , pathology , neovascularization , receptor , population , biology , chemistry , cancer research , medicine , biochemistry , environmental health
Medulloblastoma is a neuroepithelial rapidly growing tumor originating from primitive neuroectodermal tissue. It accounts for approximately 12–25% of brain tumors in pediatric population, being the most common primary solid brain tumor in children, with a strong male preponderance. Vascular proliferation may be present but is not a constant feature of this lesion, but as in other tumors neovascularization is an important mechanism underlying medulloblastoma progression and poor prognosis of the disease. Recently, the set of angiogenic mediators derived from fragments of detroyed host necrotic cells has gained scientific attention. These so‐called damage‐associated molecular pattern (DAMP) molecules activate target cells via multiple surface receptors including TLR2 and RAGE. In addition, numerous MC in the surrounding of solid tumors are a source of many compounds that are potentially involved in tumor angiogenesis. The aim of the study was to examine the expression of TLR2 and RAGE receptors and the distribution of MC associated with the tumor neovascularization in medulloblastoma of the human brain. Immunohistochemical stainings of TLR2, RAGE and MC were performed using specific primary antibodies and immunoreactions were visualized using biotinylated secondary antibodies and ABComplex/HRP or an alkaline phosphatase‐avidin‐biotin conjugate. Then, sections were lightly counterstained with Mayer's hematoxylin and the mean expression of TLR2 and RAGE as well as the distribution of MC were examined in the regions of interest (ROIs) using quantitative immunohistochemistry. Striking reduction of the MC numer by 88.9% was observed in the necrotic areas of the medulloblastoma. MC were scattered confusedly in the necrotic areas while in necrotic‐free regions, MC were numerous only in the perivascular space of large brain and meningeal vessels at the border of the tumor. The RAGE receptor was highly expressed in the endothelium of all capillaries within necrosis‐free regions of medulloblastoma. Immunohistochemistry revealed that in the tumor necrotic area, TLR acccompanies vascular network formation. However, the capillary network in the necrosis‐free regions was TLR2 immunonegative. It can thus be concluded that TLR2 plays an significant role in the recognition of ligands released from necrotic medulloblastoma cells and participates in tumor neovascularization. The RAGE receptor and MC operate almost exclusively in necrotic‐free regions of medulloblastoma influencing different parts of the tumor vascular network. Support or Funding Information WUM grant: 2M2‐W1‐16/2M2‐W2‐17 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .