Abstract

BackgroundPolyploid giant cancer cells (PGCCs) contribute to solid tumor heterogeneity. This study investigated the relationships among PGCCs numbers, vasculogenic mimicry (VM) formation, and tumor grades in glioma.MethodsA total of 76 paraffin-embedded glioma tissue samples, including 28 cases of low grade and 48 cases of high grade gliomas, were performed with H&E and immunohistochemical staining for Ki-67 and hemoglobin. The size of PGCCs nuclei was measured by a micrometer using H&E section and defined as at least three times larger than the nuclei of regular diploid cancer cells. The number of PGCCs and different blood supply patterns were compared in different grade gliomas. Microcirculation patterns in tumors were assessed using CD31 immunohistochemical and PAS histochemical double staining. Human glioma cancer cell line C6 was injected into the chicken embryonating eggs to form xenografts, which was used to observe the PGCCs and microcirculation patterns.ResultsIn human glioma, the number of PGCCs increased with the grade of tumors (χ2 = 4.781, P = 0.015). There were three kinds of microcirculation pattern in human glioma including VM, mosaic vessel (MV) and endothelium dependent vessel. PGCCs were able to generate erythrocytes via budding to form VM. The walls of VM were positive (or negative) for PAS staining and negative for CD31 staining. There were more VM and MVs in high grade gliomas than those in low grade gliomas. The differences have statistical significances for VM (t = 3.745, P = 0.000) and MVs (t = 4.789, P = 0.000). PGCCs, VM and MVs can also be observed in C6 chicken embryonating eggs xenografts.ConclusionsThe data demonstrated presence of PGCCs, VM and MVs in glioma and PGCCs generating erythrocytes contribute the formation of VM and MVs.

Highlights

  • Polyploid giant cancer cells (PGCCs) contribute to solid tumor heterogeneity

  • Cancer development usually undergoes an initial period of avascular growth followed by vasculogenic mimicry (VM) and mosaic vessels (MVs) that connect with endothelium dependent vessels to obtain sufficient blood and oxygen supply to support tumor cell growth, invasion, and metastasis [13,14]

  • Number of PGCCs associated with histologic grade of gliomas To grade all these 76 cases of glioma, new sections were cut from 76 paraffin-embedded glioma samples and stained with H&E and immunohistochemistry for further analysis

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Summary

Introduction

This study investigated the relationships among PGCCs numbers, vasculogenic mimicry (VM) formation, and tumor grades in glioma. Cancer development usually undergoes an initial period of avascular growth followed by vasculogenic mimicry (VM) and mosaic vessels (MVs) that connect with endothelium dependent vessels to obtain sufficient blood and oxygen supply to support tumor cell growth, invasion, and metastasis [13,14]. More aggressive tumors require more blood supply to support their rapid cell growth than that in the low grade tumors. Accumulating evidences have demonstrated that high grade malignant tumors including inflammatory breast cancer [15], prostate cancer [16], and invasive ovarian cancer [17], sarcoma [18,19], and hepatocellular carcinoma [14] utilize VM to support tumor cell growth, invasion and metastasis. Since tumor cells can generate erythrocytes, it is no doubt that tumor cells and their generating erythrocytes can form VM structure during tumor development and progression

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