Nestin-Expressing Cells in the Lung: The Bad and the Good Parts

Abstract

Nestin is a member of the intermediate filament family, which is expressed in a variety of stem or progenitor cells as well as in several types of malignancies. Nestin might be involved in tissue homeostasis or repair, but its expression has also been associated with processes that lead to a poor prognosis in various types of cancer. In this article, we review the literature related to the effect of nestin expression in the lung. According to most of the reports in the literature, nestin expression in lung cancer leads to an aggressive phenotype and resistance to chemotherapy as well as radiation treatments due to the upregulation of phenomena such as cell proliferation, angiogenesis, and metastasis. Furthermore, nestin may be involved in the pathogenesis of some non-cancer-related lung diseases. On the other hand, evidence also indicates that nestin-positive cells may have a role in lung homeostasis and be capable of generating various types of lung tissues. More research is necessary to establish the true value of nestin expression as a prognostic factor and therapeutic target in lung cancer in addition to its usefulness in therapeutic approaches for pulmonary diseases.

Keywords: cancer; cancer stem cells; cell therapy; lung; mesenchymal stem cells; nestin.

Figure 1

Nestin’s structure consists of a central α-helical rod domain (blue) flanked by globular NH (green) and COOH (red) domains. The α-helical rod domain consists of segments 1A and 1B separated by linker L1 and segments 2A and 2B with linker L2 between them, separated from 1B by linker L12.

Figure 2

Stem cells are capable of generating more cells of the same type by self-renewal and progenitor cells by differentiation, which, in turn, originate several types of differentiated cells. Cancer stem cells (CSCs) are generated from normal stem cells after epigenetic mutations occur. Oncogenic events include the activation of proto-oncogenes in addition to the inactivation of tumor suppressor genes and DNA repair mechanisms. CSCs are capable of self-renewal and generating daughter cells (mutated progenitors) that have more limited self-renewal ability and can originate cancer cells.