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Hyperplasia of pericytes is one of the main characteristics of microvascular architecture in malignant glioma.

Sun H, Guo D, Su Y, Yu D, Wang Q, Wang T, Zhou Q, Ran X, Zou Z - PLoS ONE (2014)

Bottom Line: The expression of PDGFβ was also scored after immunostaining.The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression.It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, China; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.

ABSTRACT

Objectives: To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma.

Methods: Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFβ was also scored after immunostaining.

Results: In grade II glioma, most of tumor MVs were the thin-wall CD34+ vessels with near normal morphology. In addition to thin-wall CD34+ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA+ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA+ MVND, CD34+ MVND and MPND were significantly augmented although the increase of CD34+ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFβ was upregulated and directly correlated with the MPND in different glioma grades.

Conclusion: Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma.

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The morphology changes of glioma microvasculature along with the increase of the WHO grade.(A) thin-wall or sinusoid vessels with different sizes of lumen in grade II glioma, (B-C) irregular buds, cell cords and thick-wall vessels in some areas of grade III glioma, (D-H) strip cord, plexus, glomeruloid, ophidian microvessels in grade IV glioma and (I) more proliferation of heterotypical vessels found around necrotic and hemorrhagic areas in grade IV glioma. (HE A-G Bar = 100 um, H and I Bar = 200 um).
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pone-0114246-g001: The morphology changes of glioma microvasculature along with the increase of the WHO grade.(A) thin-wall or sinusoid vessels with different sizes of lumen in grade II glioma, (B-C) irregular buds, cell cords and thick-wall vessels in some areas of grade III glioma, (D-H) strip cord, plexus, glomeruloid, ophidian microvessels in grade IV glioma and (I) more proliferation of heterotypical vessels found around necrotic and hemorrhagic areas in grade IV glioma. (HE A-G Bar = 100 um, H and I Bar = 200 um).

Mentions: Generally, the MV numbers and the multiplicity and complexity of the vasculatures in tumor stroma increased with the malignant grades of glioma. Less MV number and relatively normal structure were identified in grade II glioma of WHO classification, in which often seen were the thin-wall or sinusoid vessels with different sizes of lumen (Fig. 1A). In grade III glioma, besides the thin-wall vessels as above, irregular shape vessels like buds or cell cords and thick-wall vessels appeared in some areas (Fig. 1B, C). In grade IV, the most malignant glioma, high multiplicity of microvasculature was represented by the plexus, strip cords, ophidian and glomeruloid MVs (Fig. 1D-H). In some areas, these irregular vasculatures filled up almost all of the stromal spaces. It was worthy of note that the lumen of these vessels was not enlarged and even shrunk in some vessels, and that the increase of MV area was due to the hyperplasia of vascular wall cells. This heterotypical vessel morphology was quite often in high grade glioma around necrotic and hemorrhagic areas (Fig. 1 I).


Hyperplasia of pericytes is one of the main characteristics of microvascular architecture in malignant glioma.

Sun H, Guo D, Su Y, Yu D, Wang Q, Wang T, Zhou Q, Ran X, Zou Z - PLoS ONE (2014)

The morphology changes of glioma microvasculature along with the increase of the WHO grade.(A) thin-wall or sinusoid vessels with different sizes of lumen in grade II glioma, (B-C) irregular buds, cell cords and thick-wall vessels in some areas of grade III glioma, (D-H) strip cord, plexus, glomeruloid, ophidian microvessels in grade IV glioma and (I) more proliferation of heterotypical vessels found around necrotic and hemorrhagic areas in grade IV glioma. (HE A-G Bar = 100 um, H and I Bar = 200 um).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257691&req=5

pone-0114246-g001: The morphology changes of glioma microvasculature along with the increase of the WHO grade.(A) thin-wall or sinusoid vessels with different sizes of lumen in grade II glioma, (B-C) irregular buds, cell cords and thick-wall vessels in some areas of grade III glioma, (D-H) strip cord, plexus, glomeruloid, ophidian microvessels in grade IV glioma and (I) more proliferation of heterotypical vessels found around necrotic and hemorrhagic areas in grade IV glioma. (HE A-G Bar = 100 um, H and I Bar = 200 um).
Mentions: Generally, the MV numbers and the multiplicity and complexity of the vasculatures in tumor stroma increased with the malignant grades of glioma. Less MV number and relatively normal structure were identified in grade II glioma of WHO classification, in which often seen were the thin-wall or sinusoid vessels with different sizes of lumen (Fig. 1A). In grade III glioma, besides the thin-wall vessels as above, irregular shape vessels like buds or cell cords and thick-wall vessels appeared in some areas (Fig. 1B, C). In grade IV, the most malignant glioma, high multiplicity of microvasculature was represented by the plexus, strip cords, ophidian and glomeruloid MVs (Fig. 1D-H). In some areas, these irregular vasculatures filled up almost all of the stromal spaces. It was worthy of note that the lumen of these vessels was not enlarged and even shrunk in some vessels, and that the increase of MV area was due to the hyperplasia of vascular wall cells. This heterotypical vessel morphology was quite often in high grade glioma around necrotic and hemorrhagic areas (Fig. 1 I).

Bottom Line: The expression of PDGFβ was also scored after immunostaining.The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression.It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, China; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.

ABSTRACT

Objectives: To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma.

Methods: Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFβ was also scored after immunostaining.

Results: In grade II glioma, most of tumor MVs were the thin-wall CD34+ vessels with near normal morphology. In addition to thin-wall CD34+ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA+ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA+ MVND, CD34+ MVND and MPND were significantly augmented although the increase of CD34+ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFβ was upregulated and directly correlated with the MPND in different glioma grades.

Conclusion: Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma.

Show MeSH
Related in: MedlinePlus