| Malignant gliomas, accounting for 45%-50% of intracranial neoplasm, are the most common and lethal primary brain tumors. Malignant gliomas are poorly differentiated, highly proliferated and aggressive. Being the primary reason for tumor recurrence and dissemination, the ability to invade and spread into normal brain tissue obscures the histological boundary between the malignant glioma and healthy brain, and renders difficulties to surgical removal and other adjuvant therapies. Therefore, insight into the underlying biological features of invasion and migration of malignant glioma continues the urgent problem.Previous studies have shown that there are two main invasive paths for malignant glioma:one is along the myelinated nerve fibers, which is the primary way for glioma cells moving; the other is along the basement membrane of blood vessels. The formation of new blood vessels are the induced structures for tumor cell diffusing. The studies on molecular mechanism of invasiveness of malignant glioma cells suggested that the invasion of malignant gliomas is a complicate and consecutive process undergoing adhesion, degradation and migration multi-step, and involving multi-factor such as cell adhesion, molecules, enzymes, cytokines, gene regulation and angiogenesis, etc.In recent years, the glioma stem cells are identified and isolated successfully, using bio-markers, such as CD 133 and Nestin. In the glioma stem cells, more invasive subpopulation are thought to exist, which might be the root cause of tumor recurrence and migration. These findings provided a novel clue to investigate biological characteristics of invasion of malignant gliomas. To understand deeply the invasive path of glioma stem cells within the tumor and surrounding tissue, we focused on the expression of CD133, a marker for glioma stem cells, and CD34, a marker for endothelial cells, in different parts of glioblastoma tissue and tumor margin in the present study.The correlation between CD133 positive cells and CD34 positive microvascular proliferation was analyzed. The study including three parts:1. The expression of CD133 in different parts within the tumor and surrounding tissue was detected by immunohistochemistry and western blotting. No expression of CD133 was found in the control brain tissue. The expression scores of CD133 were 7.26±1.35,5.18±1.12,2.67±0.98 by immunohistochemistry, while 0.79±0.03, 0.38±0.01,0.20±0.04 by western blot, respectively in tumor marginal zones, tumor cores, and edematous zones. The difference of CD133 expression in different groups are significant statistically (P<0.05). Under the microscope, CD133-positive cells densely congregated around the vessels and formed perivascular pseudorosettes in tumor marginal zones. In the core of the tumor, CD 133 positive cells clustered around the vessels and occasionally led to pesudopalisades around necrosis. In the edematous zones, perivascular pseudorosettes of CD133 positive cells scattered and CD133 positive cells were also observed to line up along myelinated nerve fibers and the basement membrane of vessels.2. The microvessel density (MVD) in different parts within the tumor and surrounding tissue was determined by CD34 immunohistostaining. Under the microscope (magnification×200). CD34+MVD/HP were 31.32±3.97,21.80±2.58,15.28±2.37,4.67±1.53 respectively in tumor marginal zones, tumor cores, edematous areas and the control brain tissues. The difference of the microvessel density in different groups were significant statistically (P<0.05). Compared with in the control brain tissue, besides the increased microvessel density, most of those microvessels in the tumor and tumor margin were immature morphologically, only composed of a single layer of endothelial cells and lost of basement membrane, even with the cleft wall.3. The correlation was analyzed statistically between the distribution of CD 133 positive glioma stem cells and CD34+ microvascular proliferation. The expression level of CD133+ was positively correlated with CD34+MVD (r=0.928, P<0.05) in glioblastoma.Conclusion:1. The glioma stem cells tend to congregate in the tumor margin zones where the microvessels are also enriched. It suggests the glioma stem cells tropism for microvessels.2. Glioma stem cells would invade along the myelinated nerve fibers and the basement membrane of vessels within the parenchyma of the brain. 3. Blocking Glioma stem cells tropism for microvessels would be the novel strategy to prevent migration of Glioma stem cells.4. Antiangogenesis therapy might be one of efficient anti-tumor management. |
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