Tumour Stem Cells&The Evidence and the Ambiguity

Abstract

Progressive growth of malignant tumours, metastatic spread and local recurrence after treatment can only be explained by the presence of cells with unlimited proliferative ability. While this is generally accepted, the proportion of such cells and their organization in a hierarchical system of stem cells and non-stem cell progeny is still a matter of controversy. Results of quantitative transplantation and dose requirement of curative radiotherapy have indicated low stem cell fractions in human and early passage rodent tumours, but uncertainty is introduced by uncontrollable experimental or biological factors and the probabilistic nature of stem cell performance itself Studies using a particular mouse carcinoma (AT17) have given direct insight into the number and clonal expansion of stem cells in situ, strongly supporting the hierarchical concept. The implications are important and concern the relevance of predictive assays, possible mechanisms of accelerated repopulation, or the role of adjuvant treatment strategies.

Repopulation of tumor cells during fractionated radiotherapy and detection methods (Review)

“…The anticancer effect of radiotherapy is applied through the accumulation of DNA damage in the tumor cells, which may result in acute or delayed cell death known as mitotic catastrophe. Therefore, measuring tumor cell proliferation, as assessed by the uptake of markers of DNA synthesis, such as BrdUrd, or by using flow cytometry to measure DNA content, may not distinguish viable cells from those destined to die during fractionated radiotherapy (25). Also, immunohistochemical staining methods require tissue samples and are therefore invasive and limited by sampling variability.…”

A New Look at Proliferation

“…Although Julie did not directly state her disbelief in stem cells, she argued that 'there is a gross logical inconsistency in believing a small invisible, unidenti able subset determines treatment outcome, and nevertheless measuring features of the large irrelevant mass if the stem cell concept is accepted'. It is important to address this issue, as the existence of stem cells would cast serious doubt over the validity of gross measurements of tumour biopsies for prognostic indicators (see also (26), this issue).…”

Mathematical Optimization of the Combination of Radiation and Differentiation Therapies for Cancer

“…Dingli and Michor (2006) attested as title of their 2006 paper that “ Successful therapy must eradicate cancer stem cells .” This is hard to do, since CSC can be found at any location in the tumor (Youssefpour et al, 2012) and they are difficult to identify in vivo (Kummermehr, 2001). Furthermore, cancer stem cells are less sensitive to radiation or other cell killing agents (Kim and Tannock, 2005; Pajonk et al, 2010).…”