Mechanisms of cancer metastasis: involvement of cancer stem cells?

The leading cause of death from cancer is tumor expansion, which usually leads to dissemination and metastasis of malignant cells. Accumulating evidence suggests growing tumors contain some very rare primitive cells that are mobile and thus endowed with metastatic potential. If these cells survive radio/chemotherapy, they are responsible for tumor re-growth after treatment. In this review, we discuss the origin of these cells, which: 1) are true cancer stem cells (CSCs) that initiate tumor growth and are subsequently responsible for metastatic dissemination; or 2) are derived from transformed tumor cells by the epithelial mesenchymal transition phenomenon. We also address major molecular mechanisms involved in trafficking of these cells during metastasis, paying special attention to the underappreciated side effects of radio/chemotherapy that may induce pro-metastatic environments in various organs. Overall, we envision that the process of pathological metastasis of cancer cells reflects a physiological property of normal SCs for their ability to migrate, as seen during embryogenesis. Finally, we discovered highly migratory, very small embryonic-like SCs that are deposited during development in adult tissues. As we hypothesize, these cells could: 1) give rise to some primitive types of tumors; and 2) may have a direct role in cancer expansion by being involved in tumor angiogenesis and formation of tumor stroma.