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

Tumors in the rat brain. Immunocytochemical antibody staining for PCNA in the neoplastic nodule (A) 20 and (B) 30 days after implantation. (C) Area of tumor invasion into the brain parenchyma on day 20 after implantation. (D) PCNA-positive cell performance dynamics in the neoplastic nodule over time. *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. PCNA, proliferating cell nuclear antigen.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ol-0-0-4886: Tumors in the rat brain. Immunocytochemical antibody staining for PCNA in the neoplastic nodule (A) 20 and (B) 30 days after implantation. (C) Area of tumor invasion into the brain parenchyma on day 20 after implantation. (D) PCNA-positive cell performance dynamics in the neoplastic nodule over time. *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. PCNA, proliferating cell nuclear antigen.

Mentions: PCNA antibody staining was used to indicate the extent of proliferation (Fig. 3A-D). PCNA staining revealed a sharp increase in the proliferation speed of the tumor nodule on day 20 compared with day 10 that may be associated with the intensification of tumor cell division due to the development of the neoplastic blood supply network (Fig. 3A and D). Outside the tumor nidus, the maximum proportion of PCNA-positive cells was concentrated in the adjacent tissues, satellite nodules and blood vessels (data not shown). By day 30, the number of proliferating cells in the tumor tissue significantly decreased (Fig. 3В and D). Furthermore, by day 20, PCNA-positive cells had been located along the tumor borders in areas of the brain with the maximum infiltration of glioma cells due to their invasive growth (Fig. 3С). Stand-alone proliferating cells were observed in the brain tissue a significant distance from the tumor nidus (data not shown).


Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth
Tumors in the rat brain. Immunocytochemical antibody staining for PCNA in the neoplastic nodule (A) 20 and (B) 30 days after implantation. (C) Area of tumor invasion into the brain parenchyma on day 20 after implantation. (D) PCNA-positive cell performance dynamics in the neoplastic nodule over time. *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. PCNA, proliferating cell nuclear antigen.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ol-0-0-4886: Tumors in the rat brain. Immunocytochemical antibody staining for PCNA in the neoplastic nodule (A) 20 and (B) 30 days after implantation. (C) Area of tumor invasion into the brain parenchyma on day 20 after implantation. (D) PCNA-positive cell performance dynamics in the neoplastic nodule over time. *P<0.05 vs. 10 days; +P<0.05 vs. 20 days. PCNA, proliferating cell nuclear antigen.
Mentions: PCNA antibody staining was used to indicate the extent of proliferation (Fig. 3A-D). PCNA staining revealed a sharp increase in the proliferation speed of the tumor nodule on day 20 compared with day 10 that may be associated with the intensification of tumor cell division due to the development of the neoplastic blood supply network (Fig. 3A and D). Outside the tumor nidus, the maximum proportion of PCNA-positive cells was concentrated in the adjacent tissues, satellite nodules and blood vessels (data not shown). By day 30, the number of proliferating cells in the tumor tissue significantly decreased (Fig. 3В and D). Furthermore, by day 20, PCNA-positive cells had been located along the tumor borders in areas of the brain with the maximum infiltration of glioma cells due to their invasive growth (Fig. 3С). Stand-alone proliferating cells were observed in the brain tissue a significant distance from the tumor nidus (data not shown).

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