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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


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Border of neoplastic nodule in the rat brain 30 days after implantation. Immunocytochemical antibody staining against (А) nestin, (B) C-X-C chemokine receptor type 4, (C) interleukin-1β and (D) transforming growth factor-2β.
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f5-ol-0-0-4886: Border of neoplastic nodule in the rat brain 30 days after implantation. Immunocytochemical antibody staining against (А) nestin, (B) C-X-C chemokine receptor type 4, (C) interleukin-1β and (D) transforming growth factor-2β.

Mentions: The aforementioned results are due to the complex and specific interaction of microglia with tumor cells and CSCs, and are associated with the secretion of certain cytokines. On day 30, the areas of perifocal invasion with the maximum concentration of microglial cells were stained with antibodies against IL-1β, nestin, CXCR4 and TGF-2β. The tumor and near-tumor areas were heavily infiltrated with nestin; this indicated the presence of poorly differentiated cells, either CSCs or neural SCs, which, as demonstrated by the high CXCR4 expression in this location, may have migrated here. Increased expression of IL-1β was present within the tumor, and TGF-β expression was demonstrated in the near-tumor areas (Fig. 5A-D).


Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth
Border of neoplastic nodule in the rat brain 30 days after implantation. Immunocytochemical antibody staining against (А) nestin, (B) C-X-C chemokine receptor type 4, (C) interleukin-1β and (D) transforming growth factor-2β.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998210&req=5

f5-ol-0-0-4886: Border of neoplastic nodule in the rat brain 30 days after implantation. Immunocytochemical antibody staining against (А) nestin, (B) C-X-C chemokine receptor type 4, (C) interleukin-1β and (D) transforming growth factor-2β.
Mentions: The aforementioned results are due to the complex and specific interaction of microglia with tumor cells and CSCs, and are associated with the secretion of certain cytokines. On day 30, the areas of perifocal invasion with the maximum concentration of microglial cells were stained with antibodies against IL-1β, nestin, CXCR4 and TGF-2β. The tumor and near-tumor areas were heavily infiltrated with nestin; this indicated the presence of poorly differentiated cells, either CSCs or neural SCs, which, as demonstrated by the high CXCR4 expression in this location, may have migrated here. Increased expression of IL-1β was present within the tumor, and TGF-β expression was demonstrated in the near-tumor areas (Fig. 5A-D).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus