Relationship between microvessel density and cancer stem cells in tumor angiogenesis: a meta-analysis

Tumors may arise from a small subset of cancer cells that are capable of self-renewal, unlimited proliferation and tumorigenicity; such cells are termed cancer stem cells (CSCs) [1]. CSCs have been identified and isolated from tumors and tumor-derived cell lines, including melanoma [2] and brain [3], breast [4] and lung cancers [5]. It is widely accepted that angiogenesis is involved in the growth and hematogenous spread of tumors [1]. Cancer invasion and metastasis involves multiple complex steps and involves a variety of molecules. Angiogenesis, which enables the supply of blood and nutrients for tumor growth, is an important step in cancer invasion and metastasis [6,7]. According to the CSC hypothesis, CSCs play a critical role in maintaining the capacity for malignant proliferation, invasion, metastasis and recurrence of the tumor [8]. CSCs may induce cancer metastasis through multiple pathways and support tumor progression by promoting angiogenesis [9]. Therefore, accumulating evidence indicates that CSCs play a predominant role in neovascularization during tumor growth.

CSCs represent a small subpopulation of cells within a tumor that express surface markers such as CD133 [10], nestin [11], ABCG2 [12] and ALDH1 [13]. A common marker of angiogenesis, micro-vessel density (MVD) [14], has been utilized for the quantification of intratumoral angiogenesis in tumor tissue in recent years. Several vascular endothelial cell markers, such as CD31 [15] and CD34 [16], may be used for the detection of MVD. We speculate that CSCs may be involved in angiogenesis during tumor growth. Therefore, the present meta-analysis was performed to investigate the relationship between CSCs and angiogenesis by assessing MVD, which may be utilized as a clinical parameter for predicting prognosis during tumor therapy.

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