ReviewCancer stem cell: Implications in cancer biology and therapy with special reference to lung cancer
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.
Section snippets
Origin of cancer stem cells
In earlier years, it was unclear whether CSCs originate only from normal (somatic) stem cells or also from non-stem progenitors or differentiating cells. Recent evidence strongly favors a progenitor cell origin for many types of leukemic stem cells in addition to the stem cell origin [2]. In solid tumors too, it is most likely that not only somatic stem cells but also differentiating progenitor cells are capable of becoming CSCs [5]. Rapp et al. [3] proposed a model of oncogene-induced
General remarks
The compartment of CSCs comprises a very small fraction of the entire cancer cell population; thus, it is necessary to utilize specific markers, such as CD34 in several kinds of leukemia and CD44 in breast cancers, colorectal cancers, pancreas cancers, prostate cancers, head/neck cancers and some bone sarcomas, to detect and isolate CSCs from among the innumerable cancer cells and stromal cells occupying the entire tumor tissue [5], [13], [15], [16]. Representative cell surface markers for
Stem cells in healthy and injured lung
Although the airway stem cell in a strict sense has not been identified yet, several lines of evidence support the existence of regional progenitors cells, such as bronchioloalveolar progenitor cells, basal/mucous secretory bronchial progenitor cells, and neuroendocrine progenitor cells, which maintain the normal homeostasis as well as play roles for repairing injuries [63], [64], [65]. These progenitor cells expand their populations in response to various insults including toxic substances,
Conclusion and perspective
The CSC theory is tremendously attractive to both researchers and physicians, because the CSC is central to cancer cell biology and cancer therapy. The discovery of specific markers of CSCs in the respective types of cancers is particularly important. Furthermore, it is necessary to clarify the function of these molecules, as the disruption of the signaling pathways and gene transcriptions that control the activity of CSCs is the final goal of CSC-targeting therapy. We would like to emphasize
Conflict of interest statement
There is no conflict of interest.
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