Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth

Abstract

The development of antitumor medication based on autologous stem cells is one of the most advanced methods in glioblastoma multiforme (GBM) treatment. However, there are no objective criteria for evaluating the effectiveness of this medication on cancer stem cells (CSCs). One possible criterion could be a change in the number of microglial cells and their specific location in the tumor. The present study aimed to understand the interaction between microglial cells and CSCs in an experimental glioblastoma model. C6 glioma cells were used to create a glioblastoma model, as they have the immunophenotypic characteristics of CSCs. The glioma cells (0.2×106) were stereotactically implanted into the brains of 60 rats. On the 10th, 20th and 30th days after implantation, the animals were 15 of the animals were sacrificed, and the obtained materials were analyzed by morphological and immunohistochemical analysis. Implantation of glioma cells into the rat brains caused rapid development of tumors characterized by invasive growth, angiogenesis and a high rate of proliferation. The maximum concentration of microglia was observed in the tumor nodule between days 10 and 20; a high proliferation rate of cancer cells was also observed in this area. By day 30, necrosis advancement was observed and the maximum number of microglial cells was concentrated in the invasive area; the invasive area also exhibited positive staining for CSC marker antibodies. Microglial cells have a key role in the invasive growth processes of glioblastoma, as demonstrated by the location of CSCs in the areas of microglia maximum concentration. Therefore, the present study indicates that changes in microglia position and corresponding suppression of tumor growth may be objective criteria for evaluating the effectiveness of biomedical treatment against CSCs.

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

“…MMPs, CCL18, CCL22, CXCL12, IL10, TGFB, TNF, FasL, VEGF). [181][182][183][184][185] Pericytes Pericytes (PDGFRβ + , CD13 + , NG2 + , α-SMA + , Desmin + ) or Rouget cells are contractile cells located directly on small blood vessels, including capillaries, pre-capillary arterioles, and postcapillary venules. 186 The major functions of pericytes are formation of blood vessels, glial scars, and the BBB, capillary diameter, and cerebral blood flow (CBF) regulation, amyloid β clearance, and neuroinflammation suppression, and they at times exhibit stem cell-like properties.…”

Genome editing of <i>Nf1, Pten,</i> and <i>Trp53</i> in neonatal mice induces glioblastomas positive for oligodendrocyte lineage transcription factor 2

“…Similarly, Iba-1-positive cells with increased cellularity, either in or scattered around the tumor area ( Fig. 2G, N ), appeared to be reactive microglia 15 , 16 . Based on these histological and IHC results, we diagnosed the tumors as gliomas (n=4), including glioblastomas (n=3; Tables 2…”

“…Similarly, Iba-1-positive cells with increased cellularity, either in or scattered around the tumor area (Fig. 2G, N), appeared to be reactive microglia 15,16 .…”

The Dr. Jekyll and Mr. Hyde complexity of the macrophage response in disease

“…Recent studies have shown that gliomas cause reduced caspase-3 activity in microglia via an iNOS-based mechanism, resulting in tumor growth. In addition, it is thought that microglia directly support cancer stem cell growth in glioblastoma multiforme, contributing to its aggressive progression and resistance to treatment [48].…”