Abstract
Glial dysfunction outraging CNS plasticity and integrity results in one of the most dangerous cancers, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not properly related so far. The present study is aimed to find a relationship between this featured quadrangle from lower to higher grades (HG) of post-operative glioma tissues and their invading subsets. Elevated Ki67-associated proliferation in lower grades (LG) was supported with VEGF dependent angiogenic maintenance which found a decrease unlikely in HG. In contrast, MMP 2 and 9-associated invasions augmented high in HG with the dominant presence of CD204+ M2 polarized macrophages and a general increase in global DNMT1-associated methylation. Marked differences found in ECM invading cellular subsets of HG showing high proliferative capacity indicating rationally for recurrence, contrasting the nature of gross tumor tissue of the same grade. Thus in LG, the neoplastic lesion is more inclined to its growth while in higher grade more disposed towards tissue wreckage in support with cellular environmental milieu whereas the cellular variants and subsets of invaded cells showed different trends. Therefore, some operational dichotomy or coupling among cellular variants in glioma is active in determining its low- to high-grade transition and aggressive progression.
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Acknowledgements
Acknowledging M.Ch students at Neurosurgery unit, BIN, IPGME&R for post-operative tumor samples, Dr. Ritesh Tiwari of BD-CoE Flow Cytometry unit at CRNN, University of Calcutta for immuno-flowcytometry experiments and analysis. Sincere gratitude to Prof. Asis Kumar Chattopadhyay and Ms. Soumita Modak, Department of Statistics, University of Calcutta for helping in statistical interpretation. Authors also thank Mr. Sanku Mondal and Mr. Abir Roy for their suggestions in preparing the figures for the manuscript.
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This work was supported by the Council of Scientific and Industrial Research (CSIR), Government of India for financial aid vide Sanction No. 37(1587)/13/EMR-II dated 01.04.2013 to Anirban Ghosh as Principal Investigator (PI) for the work.
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KG primarily performed the experiments as designed by AG, acquired and analyzed data and drafted the initial manuscript; SG provided post-surgical samples and MRI data; UC have done histopathological analysis; PB provided few experimental facilities to KG and mentored him; AG planned the whole work with acquisition of fund, mentored KG and supervised the whole work and experiments, analyzed data and finalized the manuscript draft.
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Working with the post-operative human tumor samples, authors abide by patients’ consent proposal and Human Ethical Clearance (Memo No: Inst/IEC/553 dated 15.01.2014) from Institutional Ethical Committee (IEC) at Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, West Bengal, India legally validating World Medical Association (WMA), Declaration of Helsinki.
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10571_2021_1096_MOESM1_ESM.tiff
Supplementary file1 (TIFF 2376 KB) Supplementary Figure S1 72 hours primary glioma cell culture from patient samples of low and high-grade gliomas at ×1 DMEM with 15% FBS and 2% antibiotic medium at 37 °C, 5% CO2 humidified cell culture incubator. After successive washing with 1× PBS buffer, cells were used for an array of studies. Photographs are taken under phase-contrast light microscopy at ×400, TS 100-F Eclipse, Nikon Corp., Japan.
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Ghosh, K., Ghosh, S., Chatterjee, U. et al. Dichotomy in Growth and Invasion from Low- to High-Grade Glioma Cellular Variants. Cell Mol Neurobiol 42, 2219–2234 (2022). https://doi.org/10.1007/s10571-021-01096-1
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DOI: https://doi.org/10.1007/s10571-021-01096-1