Limits...
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.


Related in: MedlinePlus

Tumor in the rat brain. Immunocytochemical antibody staining for IBA-1 (microglia/macrophage-specific protein) in (A) the neoplastic nodule, (B) the brain area adjacent to the nodule and (C) the brain area of the hemisphere opposite to the nodule 20 days after implantation, and in (D) the neoplastic nodule 30 days after implantation. (E) Staining with hematoxylin and eosin and IBA-1 antibody revealed IBA-positive cells on the border of the neoplastic nodule on day 30 after implantation. (F) IBA-1-positive cell performance dynamics in neoplastic nodule over time *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. IBA-1, ionized calcium-binding adapter molecule-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998210&req=5

f4-ol-0-0-4886: Tumor in the rat brain. Immunocytochemical antibody staining for IBA-1 (microglia/macrophage-specific protein) in (A) the neoplastic nodule, (B) the brain area adjacent to the nodule and (C) the brain area of the hemisphere opposite to the nodule 20 days after implantation, and in (D) the neoplastic nodule 30 days after implantation. (E) Staining with hematoxylin and eosin and IBA-1 antibody revealed IBA-positive cells on the border of the neoplastic nodule on day 30 after implantation. (F) IBA-1-positive cell performance dynamics in neoplastic nodule over time *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. IBA-1, ionized calcium-binding adapter molecule-1.

Mentions: The maximum concentration of microglial cells was observed in the tumor tissue itself and adjacent glioma invasion areas on days 10–20, as opposed to in tissues from the opposite hemisphere of the brain (Fig. 4A-F). Significant clusters of small IBA-1-positive cells with an elongated shape and short extensions were concentrated in the brain parenchyma a small distance from the tumor nodule and in the endothelium of hypertrophied blood vessels (Fig. 4B). The changes in microglial cell concentration in the neoplastic nodule between days 10 and 20 may be caused by the transformation of monocytes migrating from the newly formed capillaries into resident macrophages, as well as by the local migration of microglia from the adjacent brain tissues. The number of IBA-1-positive cells in the brain parenchyma of the hemisphere containing the tumor was significantly larger than the number in the intact (opposite) hemisphere 20 days after implantation (Fig. 4С and F).


Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth
Tumor in the rat brain. Immunocytochemical antibody staining for IBA-1 (microglia/macrophage-specific protein) in (A) the neoplastic nodule, (B) the brain area adjacent to the nodule and (C) the brain area of the hemisphere opposite to the nodule 20 days after implantation, and in (D) the neoplastic nodule 30 days after implantation. (E) Staining with hematoxylin and eosin and IBA-1 antibody revealed IBA-positive cells on the border of the neoplastic nodule on day 30 after implantation. (F) IBA-1-positive cell performance dynamics in neoplastic nodule over time *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. IBA-1, ionized calcium-binding adapter molecule-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ol-0-0-4886: Tumor in the rat brain. Immunocytochemical antibody staining for IBA-1 (microglia/macrophage-specific protein) in (A) the neoplastic nodule, (B) the brain area adjacent to the nodule and (C) the brain area of the hemisphere opposite to the nodule 20 days after implantation, and in (D) the neoplastic nodule 30 days after implantation. (E) Staining with hematoxylin and eosin and IBA-1 antibody revealed IBA-positive cells on the border of the neoplastic nodule on day 30 after implantation. (F) IBA-1-positive cell performance dynamics in neoplastic nodule over time *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. IBA-1, ionized calcium-binding adapter molecule-1.
Mentions: The maximum concentration of microglial cells was observed in the tumor tissue itself and adjacent glioma invasion areas on days 10–20, as opposed to in tissues from the opposite hemisphere of the brain (Fig. 4A-F). Significant clusters of small IBA-1-positive cells with an elongated shape and short extensions were concentrated in the brain parenchyma a small distance from the tumor nodule and in the endothelium of hypertrophied blood vessels (Fig. 4B). The changes in microglial cell concentration in the neoplastic nodule between days 10 and 20 may be caused by the transformation of monocytes migrating from the newly formed capillaries into resident macrophages, as well as by the local migration of microglia from the adjacent brain tissues. The number of IBA-1-positive cells in the brain parenchyma of the hemisphere containing the tumor was significantly larger than the number in the intact (opposite) hemisphere 20 days after implantation (Fig. 4С and F).

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&times;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