Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven

Hill, Richard P.

doi:10.1158/0008-5472.can-05-3450

Cited by 230 publications

(169 citation statements)

References 35 publications

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“…The number of cells that are terminally differentiated is increasing over time, reaching a steady level that is comparable to normal growth, see Figure 6. Note that in both normal and benign tumor cases, the total stem cell population consisting of quiescent and progenitor populations is 5%, which is in agreement with experimental values, see [1], [4], [10].…”

Section: Disease Progression and Model Predictionssupporting

confidence: 89%

Modeling the Cancer Stem Cell Hypothesis

Calmelet

Prokop

Mensah

et al. 2010

Math. Model. Nat. Phenom.

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Abstract. Solid tumors and hematological cancers contain small population of tumor cells that are believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast, prostate, pancreas, colon, brain and lung cancers. It is also thought that CSCs drive the metastatic spread of cancer. The CSC compartment features a specific and phenotypically defined cell population characterized with self-renewal (through mutations), quiescence or slow cycling, overexpression of anti-apoptotic proteins, multidrug resistance and impaired differentiation. CSCs show resistance to a number of conventional therapies, and it is believed that this explains why it is difficult to completely eradicate the disease and why recurrence is an ever-present threat. A hierarchical phenomenological model is proposed based on eight compartments following the stem cell lineage at the normal and cancer cell levels. As an empirical test, the tumor grading and progression, typically collected in the pathologic lab, is used to correlate the outcome of this model with the tumor development stages. In addition, the model is able to quantitatively account for the temporal development of the population of observed cell types. Two types of therapeutic treatment models are considered, with dose-density chemotherapy (a pulsatile scenario) as well as continuous, metronomic delivery. The drug hit is considered at the stem cell progenitor and early differentiated specialized cell levels for both normal and cancer cells, while the quiescent stem cell and fully differentiated compartments are considered favorable outcome for cancer treatment. Circulating progenitors are neglected in this analysis. The model provides a number of experimentally testable predictions. The relative importance of the cell kill and survival is demonstrated through a deterministic parametric study. The significance of the stem cell compartment is underlined based on this simulation study. This predictive mathematical model for cancer stem cell hypothesis is used

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Section: Disease Progression and Model Predictionssupporting

confidence: 89%

Modeling the Cancer Stem Cell Hypothesis

Calmelet

Prokop

Mensah

et al. 2010

Math. Model. Nat. Phenom.

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show abstract

“…Guided by current knowledge about normal stem cells, future characterizations of the origin, as well as the cellular and molecular mechanisms governing the in vivo behaviors of mCSCs, should shed light on potential therapeutic applications related to metastasis. Before proceeding, however, it is important to keep in mind that various aspects of the CSC theory remain to be unequivocally confirmed in different cancer types, particularly in solid tumors [2]. Therefore, this review should be considered as a discussion of the current status of the field and as a guide for future research rather than summaries of proven hypotheses.…”

Section: Introductionmentioning

confidence: 99%

Beyond tumorigenesis: cancer stem cells in metastasis

et al. 2006

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“…However, it has been demonstrated that the growth of secondary tumors is highly dependent on the environment to which the cells are exposed. Factors such as the location of the transplantation, the presence or absence of highly irradiated feeder cells, and the inclusion of additional extracellular matrix components significantly affect the growth potential of implanted tumor cells (Hewitt et al 1973;Peters and Hewitt 1974;Hill 2006). Prostate cancer is the most commonly diagnosed cancer and the second highest cancer-related cause of death among men.…”

mentioning

confidence: 99%

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Lukacs¹,

Lawson²,

Long-zuo³

et al. 2008

Cold Spring Harbor Symposia on Quantitative Biology

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Prostate cancer is a leading cause of cancer-related death in adult men. It can regress dramatically upon antihormonal therapy, but it often recurs in a more aggressive, androgen-independent form. Defining the prostate tissue stem cells (PrSCs) and their involvement in cancer initiation and maintenance may lead to better therapeutics. Using a tissue-regeneration model in which dissociated prostate epithelial cells mixed with inductive mesenchyme give rise to prostatic tubules, we have identified a small population of prostate cells that contains multiple stem cell characteristics. In this system, prostate cancer can be initiated by autocrine or paracrine growth factor signaling and intracellular overexpression of genes often found mutated in human prostate cancer. Using an in vitro prostate sphere assay, we further defined the PrSC population and demonstrated their selfrenewal and multilineage differentiation capabilities. Microarray analyses of the stem-and non-stem-cell populations have assisted us in finding and evaluating additional markers that can better define the PrSC population and further delineate the different cell types of the prostate, including those that serve as the target cell for tumor initiation.

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Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven

Cited by 230 publications

References 35 publications

Modeling the Cancer Stem Cell Hypothesis

Modeling the Cancer Stem Cell Hypothesis

Beyond tumorigenesis: cancer stem cells in metastasis

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

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