Differentiation and transdifferentiation potentials of cancer stem cells.

// Zhengjie Huang 1,2,* , Tiantian Wu 2,* , Allan Yi Liu 2 and Gaoliang Ouyang 2 1 Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China 2 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China * These authors have contributed equally to this article Correspondence to: Gaoliang Ouyang, email: // Allan Yi Liu, email: // Keywords : cancer stem cell, differentiation, transdifferentiation, stromal cells, tumor microenvironment Received : May 13, 2015 Accepted : September 05, 2015 Published : October 12, 2015 Abstract Tumor cells actively contribute to constructing their own microenvironment during tumorigenesis and tumor progression. The tumor microenvironment contains multiple types of stromal cells that work together with the extracellular matrix and local and systemic factors to coordinately contribute to tumor initiation and progression. Tumor cells and their stromal compartments acquire many genetic and/or epigenetic alternations to facilitate tumor growth and metastasis. The cancer stem cell (CSC) concept has been widely applied to interpreting tumor initiation, growth, metastasis, dormancy and relapse. CSCs have differentiation abilities to generate the original lineage cells that are similar to their normal stem cell counterparts. Interestingly, recent evidence demonstrates that CSCs also have the potential to transdifferentiate into vascular endothelial cells and pericytes, indicating that CSCs can transdifferentiate into other lineage cells for promoting tumor growth and metastasis in some tissue contexts instead of only recruiting stromal cells from local or distant tissues. Although the transdifferentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity, many aspects of CSC transdifferentiation remain elusive. In this review, we summarize the multi-lineage differentiation and transdifferentiation potentials of CSCs as well as discuss their potential contributions to tumor heterogeneity and tumor microenvironment in tumor progression.