Lung cancer stem cell: new insights on experimental models and preclinical data

Abstract

Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developing in vitro and in vivo models may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies.

Figure 1

Lung CSCs and progenitors which differentiation leads to heterogeneity of associated human carcinomas. Normal and tumor cellular hierarchy progressively generates progenitor cells and differentiated mature cells in both proximal and distal airways. Hypotheses are represented with discontinuous lines.

Figure 2

In vitro models of lung CSCs. Experimental models of lung CSCs are based on the functional properties of chemoresistance of these cells or on their phenotypic characteristics. Populations enriched in CSCs obtained after treatment or cell sorting need to present all the stemcellness properties to be considered as lung CSC models.

Figure 3

CSC and lung CSC properties. CSC characteristics verified on lung CSC models are presented with the references of the corresponding reports.