AccScience Publishing / EJMO / Volume 5 / Issue 1 / DOI: 10.14744/ejmo.2021.79703
RESEARCH ARTICLE

Association Between Macrophages with Angiogenic Cells and Microvascular Dysfunction in Astrocytic Glioma

Priscilla Das1 Nyi Nyi Naing2 Nadiah Wan-Arfah2 Kon Noorjan4 Yee Cheng Kueh5 Kantha Rasalingam6
Show Less
1 Department of Unit of Biostatistics & Research, Faculty of Medicine, SEGi University, Kota Damansara, Petaling Jaya, Selangor, Malaysia; Department of Methodology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan
2 Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Jalan Sultan Mahmud, Kuala Terengganu, Terengganu, Malaysia
3 Faculty of Health Sciences Universiti Sultan Zainal Abidin Gong Badak Campus, Kuala Nerus, Terengganu, Malaysia
4 Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
5 Department of Psychiatry, Unit of Biostatistics & Research Methodology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan
6 Department of Neuroscience, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur, Malaysia
Submitted: 20 January 2021 | Accepted: 19 February 2020 | Published: 25 February 2020
© 2020 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Objectives: Astrocytic gliomas are the most common primary brain tumours that developed from glial origin. Macrophages are the predominant inflammatory cells in infiltrating gliomas. The study aimed to investigate the association between circulating macrophages with tissue resident angiogenic cells and microvascular dysfunction in astrocytic glioma.

Methods: A total of 22 astrocytic glioma patients were consented from Hospital Universiti Sains Malaysia. Tumour (n=22) were sliced and stained with CD133+ and VEGFA+ angiogenic markers and counter stained with DAPI. The Spearman rho’s test was used for the data analysis. The plasma CD68, macrophage level and von Willebrand factor level or factor VIII level (vWF/ FVIII) was measured using Elisa Kit (CUSABIO BIOTECH CO., LTD).

Results: The mean plasma CD68 macrophages was 12.48±19.98 pg/ml. The mean percentage of brain tumour tissue angiogenic cells was (1.26±0.95%), adjacent normal brain tissue angiogenic cells was (0.72±0.68%). Spearman’s rho correlation test showed a significant correlation between brain tumour angiogenic cells and plasma CD68 macrophages (n=22) (Spearman’s rho, r=0.43, p=0.047). However no correlation was observed between plasma CD68 macrophages with adjacent normal brain (Spearman’s rho r =0. 019, p=0. 932). In this study vWF/FVIII level was analysed and about 14 patients with (mild factor level of >5%), 8 patients with (moderate factor level of 1-5%) and no patients had (severe factor level of <1%) was found. The mean vWF/FVIII percentage patient with mild level was 12.48±7.77 % and moderate vWF/FVIII factor level was 3.53±1.32%. The spearman’s rho correlation test showed a significant correlation between patient with moderate vWF/FVIII level with plasma CD68 macrophages (Spearman’s rho r=0.73, p=0.041).

Conclusion: Circulating macrophages associated with brain tumour angiogenic cells and vWF/FVIII of astrocytic glioma. Thus targeting these parameters in the treatment of glioma might be useful.

Keywords
Angiogenic cells
astrocytic glioma
brain tumour
macrophages
microvascular dysfunction
Conflict of interest
None declared.
References

1.Machein, M.R., et al., Minor contribution of bone marrow-derived endothelial progenitors to the vascularization of murine gliomas. Brain Pathol 2003;13:582-97. [CrossRef]

2. Parney, I.F., J.S. Waldron, and A.T. Parsa, Flow cytometry and in vitro analysis of human glioma-associated macrophages. Laboratory investigation. J Neurosurg 2009;110:572-82. [CrossRef]

3. Graf, M.R., et al., Development of systemic immunity to glioblastoma multiforme using tumor cells genetically engineered to express the membrane-associated isoform of macrophage colony-stimulating factor. J Immunol 1999;163:5544-51.

4. Hao, Q., et al., Contribution of bone marrow-derived cells associated with brain angiogenesis is primarily through leukocytes and macrophages. Arterioscler Thromb Vasc Biol 2008;28:2151-7. [CrossRef]

5. Fries G., P.A., Kempski O. , Glioblastoma associated circulating monocytes and the release of epidermal growth factor. J Neurosurg 1996;85:642-647. [CrossRef]

6. Rehman, J., et al., Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors. Circulation 2003;107:1164-1169.

7. Chen, L., et al., Increased pro-angiogenic factors, infiltrating neutrophils and CD163+ macrophages in bronchoalveolar lavage fluid from lung cancer patients. International Immunopharmacology 2014;20:74-80. [CrossRef]

8. Yi, L., et al., Glioma-initiating cells: A predominant role in microglia/macrophages tropism to glioma. Journal of Neuroimmunology 2011;232:75-82. [CrossRef]

9. Starke, R.D., et al., Endothelial von Willebrand factor regulates angiogenesis. Blood 2011;117:1071-1080. [CrossRef]

10. Verma, S., M.R. Buchanan, and T.J. Anderson, Endothelial Function Testing as a Biomarker of Vascular Disease. Circulation 2003;108:2054-2059. [CrossRef]

11. Gallinaro, L., et al., A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood 2008;111:3540-5.

12. Benedetta Bussolati, M.C.D., and Giovanni Camussi. , Characterization of molecular and functional alterations of tumor endothelial cells to design anti-angiogenic strategies. Current vascular pharmacology, 2010. [CrossRef]

13. Chi, A.S., et al., Angiogenesis as a therapeutic target in malignant gliomas. The Oncologist, 2009 14:621-636. [CrossRef]

14. Rafat N., B.G.C.H., Schulte J., Tuenttenberg J., Vajkoczi P. , Circulating endothelial progenitor cells in malignant gliomas. J Neurosurg 2010; 12:43-49. [CrossRef]

15. Greenfield, J.P., et al., Surrogate markers predict angiogenic potential and survival in patients with glioblastoma multi-forme. Neurosurgery, (10): p. 2009 May;64(5):819-26; discussion 826-7. [CrossRef]

16. Borchiellini, A., et al., Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood 1996;88:2951-8. [CrossRef]

17. Strik, H., et al., Galectin-3: Cellular Distribution and Correlation with WHO-grade in Human Gliomas. Journal of Neuro-Oncology, 2001. 53(1): p. 13-20. [CrossRef]

18. Thomas Wirth, F.A., Agnieszka Pacholska, aritha Samaranayake and Seppo Ylä- erttuala, The Syngeneic BT4 Rat Malignant Glioma is a Valuable Model to tudy Myelomonocytic ells in Tumors. Cancer Growth and Metastasis, 2012;5:19-25. [CrossRef]

19. Yao, Y., et al., Macrophage Infiltration-associated Thymidine Phosphorylase Expression Correlates with Increased Microvessel Density and Poor Prognosis in Astrocytic Tumors. Clinical Cancer Research 2001;7:4021-4026.

20. Golebiewska, A., et al., Side population in human glioblastoma is non-tumorigenic and characterizes brain endothelial cells. Brain, 2013. [CrossRef]

21. S. Farzana Hussain, D.Y., Dima Suki, Kenneth Aldape, Elizabeth Grimm, Amy B. Heimberger, The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro-oncol 2006:261-279. [CrossRef]

22. STROJNIK, T., et al., Prognostic Impact of CD68 and Kallikrein 6 in Human Glioma. Anticancer Research 2009;29:3269-3279.

Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing