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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.

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Hematoxylin and eosin staining of neoplastic tissue in the rat brain. Twenty days after implantation, (А) newly formed blood vessels were observed in the tumor tissue and (B) a blood vessel developed among tumor cells of the satellite nodule, distant from the primary nodule. Thirty days after implantation, (C) an angiocentric cluster of tumor cells developed and (D) necrotic areas were observed in the tumor tissue.
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f2-ol-0-0-4886: Hematoxylin and eosin staining of neoplastic tissue in the rat brain. Twenty days after implantation, (А) newly formed blood vessels were observed in the tumor tissue and (B) a blood vessel developed among tumor cells of the satellite nodule, distant from the primary nodule. Thirty days after implantation, (C) an angiocentric cluster of tumor cells developed and (D) necrotic areas were observed in the tumor tissue.

Mentions: An MRI scan performed 10 days after the implantation of tumor cells showed massive tumors (mean ± SEM, 5.6±1.4mm3) in the brains of all the animals. Morphological analysis revealed that the tumor was comprised of variously shaped cells with different numbers of nuclei of different sizes. By day 20, the neoplastic tissue contained a large number blood microvessels, indicating a high metabolism. At the periphery of the tumor nidus, the glioma cells invaded the brain parenchyma with dystrophic changes and the creation of chords surrounded by a large number of cells (Fig. 2А). A little farther from the primary nodule, the glioma cells were clustered into conglomerates creating secondary satellite tumors. Rapid growth of a feeding blood vessel in the center of the secondary nidus intensified neoplastic development and invasive processes (Fig. 2B).


Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth
Hematoxylin and eosin staining of neoplastic tissue in the rat brain. Twenty days after implantation, (А) newly formed blood vessels were observed in the tumor tissue and (B) a blood vessel developed among tumor cells of the satellite nodule, distant from the primary nodule. Thirty days after implantation, (C) an angiocentric cluster of tumor cells developed and (D) necrotic areas were observed in the tumor tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ol-0-0-4886: Hematoxylin and eosin staining of neoplastic tissue in the rat brain. Twenty days after implantation, (А) newly formed blood vessels were observed in the tumor tissue and (B) a blood vessel developed among tumor cells of the satellite nodule, distant from the primary nodule. Thirty days after implantation, (C) an angiocentric cluster of tumor cells developed and (D) necrotic areas were observed in the tumor tissue.
Mentions: An MRI scan performed 10 days after the implantation of tumor cells showed massive tumors (mean ± SEM, 5.6±1.4mm3) in the brains of all the animals. Morphological analysis revealed that the tumor was comprised of variously shaped cells with different numbers of nuclei of different sizes. By day 20, the neoplastic tissue contained a large number blood microvessels, indicating a high metabolism. At the periphery of the tumor nidus, the glioma cells invaded the brain parenchyma with dystrophic changes and the creation of chords surrounded by a large number of cells (Fig. 2А). A little farther from the primary nodule, the glioma cells were clustered into conglomerates creating secondary satellite tumors. Rapid growth of a feeding blood vessel in the center of the secondary nidus intensified neoplastic development and invasive processes (Fig. 2B).

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