The architect who never sleeps: tumor-induced plasticity

Abstract

Tumor cell plasticity is an event that has been observed in several malignancies. In fact, most of the solid tumors are characterized by cellular heterogeneity and undergo constant changes as the tumor develops. The increased plasticity displayed by these cells allows them to acquire additional properties, enabling epithelial-mesenchymal transitions, dedifferentiation and the acquisition of stem cell-like properties. Here we discuss the particular importance of an inflammatory microenvironment for the bidirectional control of cellular plasticity and the potential for therapeutic intervention.

Keywords: Cancer; Cell plasticity; Tumor microenvironment.

Fig. 1

NF-κB signaling exerted effects. High wnt-activity and concomitant NF-κB activation induces dedifferentiation and acquisition of stem cell-like properties. Simultaneously, NF-κB-dependent inflammatory microenvironment induces EMT promoting invasion and lymph node metastasis.

Fig. 2

Tumor plasticity. EMP, dedifferentiation, transdifferentiation and cell fusion can be viewed as the four major sources of tumor plasticity and heterogeneity during tumorigenesis. EMP enhances invasion, and metastatic dissemination. Dedifferentiation of mature cells increases stemness and is believed to contribute to therapy resistance. Transdifferentiation causes one cell type to interconvert into a different cell type and cell fusion generates hybrid cells with both epithelial and immune cell-like properties. All process share some common characteristics and similar regulatory mechanisms. The three small circles represent the three major inducers of tumor-plasticity. Mutations in most important tumor suppressors and oncogenes, epigenetic modifications and the inflammatory microenvironment are the most potent inducers of tumor cell plasticity.