Cancer stem cell: Implications in cancer biology and therapy with special reference to lung cancer

Abstract

The cancer stem cell (CSC) theory is currently central to the field of cancer research, because it is not only a matter of academic interest but also crucial in cancer therapy. CSCs share a variety of biological properties with normal somatic stem cells in terms of self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their tumorigenic activity. Thus, CSCs are also termed cancer initiating cells. In this paper, we briefly review hitherto described study results and refer to some excellent review articles to understand the basic properties of CSCs. In addition, we focus upon CSCs of lung cancers, since lung cancer is still increasing in incidence worldwide and remains the leading cause of cancer deaths. Understanding the properties of, and exploring cell markers and signaling pathways specific to, CSCs of lung cancers, will lead to progress in therapy, intervention, and improvement of the prognosis of patients with lung cancer. In the near future, the evaluation of CSCs may be a routine part of practical diagnostic pathology.

Introduction

Current investigations in the field of cancer research intensively focus upon the “cancer stem cell (CSC)”. The CSC theory appears to be well established and now widely accepted [1], [2], [3], [4], [5], [6], [7], though some controversies still remain [8], [9], [10], [11], [12], [13], [14]. The CSC, similar to a normal stem cell, is capable of self-renewal and the production of differentiated progeny. In addition, the human CSC has a capacity to form secondary/tertiary tumors upon serial xenotransplantation into immunocompromised rodents, the features of which mimic the original tumors. The demonstration of these three capacities is the golden standard to identifying human CSCs, and such features of CSCs reflect the activity of cancer initiation, recurrence, therapy-resistance, and metastasis, all of which are critical in cancer therapy. The term CSC is frequently used to mean “cancer initiating cell (CIC)”. In this article, we briefly discuss the general features of CSCs. We also focus upon the characteristics of CSCs in lung cancers, since lung cancer is the leading cause of cancer deaths worldwide and one of the most intractable cancers.