Cancer stem cells and tumor metastasis (Review)

Abstract

Previous studies have shown that tumors can induce angiogenesis and lymphangiogenesis, which plays an important role in promoting hematogenous and lymphogenous spread. In recent years, the cancer stem cell (CSC) theory has emerged as an attractive hypothesis for tumor development and progression. The theory proposes that one small subset of cancer cells has the characteristics of stem cells. These CSCs have the capability of both self-renewal and differentiation into diverse cancer cells, which play a decisive role in maintaining capacity for malignant proliferation, invasion, metastasis, and tumor recurrence. CSCs are involved in tumor metastasis, however, the details, and the possible relationship of CSCs, angiogenesis, lymphangiogenesis, and tumor metastasis is still ambiguous. The aim of this report is to summarize current studies of CSCs and tumor metastasis at the cellular level, with the goal of bringing new insights into understanding the role of CSCs in tumor metastasis.

Figure 1.

Lymphangiogenic growth factors and their receptors. Ang-1 and -2, angiopoietins-1 and -2; ET-1, endothelin-1; FGF-2, fibroblast growth factor-2; FGFR, fibroblast growth factor receptor; HGF, hepatocyte growth factor; IGF-1, -2, insulin-like growth factors-1 and -2; IGFR-1, insulin-like growth factor receptor-1; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor; TIE-2, endothelial cell-specific receptor tyrosine kinase; VEGF-A, -C and -D, vascular endothelial growth factors-A, -C and -B; VEGFR-1, -2 and -3, vascular endothelial growth factor receptors-1, -2 and -3.

Figure 2.

Proposed scheme for the relationship between cancer stem cells and lymphatic metastasis. CSCs, cancer stem cells; EMT, epithelial-mesenchymal transition; LECs, lymphatic endothelial cells; MSCs, mesenchymal stem cells.

Figure 3.

Proposed scheme for the relation of cancer stem cells and cancer metastasis. Blood endothelial cells in angiogenesis and lymphatic endothelial cells in lymphangiogenesis may be derived from different cells, including direct transdifferentiation from cancer stem cells. Cancer stem cells may also participate in angiogenesis and lymphangiogenesis through generating various angiogenic and lymphangiogenic factors. BECs, blood endothelial cells; CSCs, cancer stem cells; EMT, epithelial-mesenchymal transition; LECs, lymphatic endothelial cells; MSCs, mesenchymal stem cells; TAMs, tumor-associated macrophages.