A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer

Odoux, Christine; Fohrer, Hélène; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna B.; Lewis, Dale; Gollin, Susanne M.; Gamblin, T. Clark; Geller, David A.; Lagasse, Eric

doi:10.1158/0008-5472.can-07-5779

Cited by 152 publications

(152 citation statements)

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“…More studies are required to resolve these contradictory findings. Chen et al [66] [75][76][77][78][79][80][81][82][83][84][85][86] using cell surface markers CD133 [75][76][77], CD44 [78,79] or ABCB5 [85], clonal analysis [80], SP phenotype [84], and Aldefluor assays [82]. As in studies of BTSCs, use of CD133 as a positive selection marker for colon CSCs has generated conflicting results [75][76][77]81], but subsequent studies indicate that the AC133 epitope, but not CD133 protein, is differentially and specifically expressed in colon CSCs and its expression is lost upon differentiation [83].…”

Section: Csc Heterogeneitymentioning

confidence: 99%

“…It is conceivable that more mature tumor-initiating cells derived from the primitive CSCs may sustain secondary genetic hits and in turn become new CSCs, and then develop independently of the original CSCs. In reality, both hierarchical tumor-initiating populations and independently evolving tumorigenic clones may operate to create the heterogeneity of CSCs [80].…”

Section: Csc Heterogeneitymentioning

confidence: 99%

“…For example, although LSC activity has been detected in several cellular compartments, the most tumorigenic subpopulation is still in undifferentiated Lin -CD34 + CD38 -cells, which can develop into more mature, less tumorigenic cells [112,113,115]. Likewise, in marker-independent sphere-(e.g., neurosphere, mammosphere, colonosphere, prostasphere, etc) formation assays, it has been repeatedly demonstrated that a single (undifferentiated) tumor cell can generate a sphere that contains multiple types of lineage-differentiated cells [49,61,66,76,80,90,95,100,106]. CD133 + colon CSCs can grow exponentially for more than a year as undifferentiated tumor spheres in vitro but, upon transplantation in vivo, they can generate tumors that histologically recapitulate the morphological and antigenic pattern of the original tumor [76].…”

Section: Intrinsic and Induced Plasticity In Csc Progenymentioning

confidence: 99%

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Understanding cancer stem cell heterogeneity and plasticity

2012

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Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

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Section: Csc Heterogeneitymentioning

confidence: 99%

Section: Csc Heterogeneitymentioning

confidence: 99%

Section: Intrinsic and Induced Plasticity In Csc Progenymentioning

confidence: 99%

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Understanding cancer stem cell heterogeneity and plasticity

2012

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“…However, not all of these genetic alterations occur during the process of liver metastasis (Gray, 2010). In the initiation model, cells with metastatic potential are determined by early mutational events in a progenitor cell, named cancer stem cell (CSCs) or tumor-initiating cells (TIC; Clarke and Fuller, 2006;Polyak and Hahn, 2006;Odoux et al, 2008), even if few data support the hypothesis of its role in the colon metastatic process in humans (Horst et al, 2009b;Puglisi et al, 2009;Ju et al, 2011).CD44 and CD133 have already been validated as informative markers of stem cells in both primary tumors and xenografts (O'Brien et al, 2007;Ricci-Vitiani et al, 2007). CD133, originally known as AC133, is a glycoprotein also known in humans and rodents as Prominin 1 (PROM1; Kawamoto et al, …”

mentioning

confidence: 99%

Co‐expression of CD133⁺/CD44⁺ in human colon cancer and liver metastasis

Bellizzi¹,

Sebastian²,

Ceglia³

et al. 2012

Journal Cellular Physiology

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Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, non-tumor tissue and liver metastasis were obtained directly from the operating room, examined, and immediately processed. CSCs were selected under serum-free conditions and characterized by CD44 and CD133 expression levels. CD133þ /CD44 þ cell populations were then investigated in paraffin-embedded tissues and circulating tumor cells isolated from peripheral blood of the same group of colon cancer patients. Our data demonstrate that metastatic properties of cell populations from blood and liver metastasis, differently from primitive tumors, seem to be strictly related to the phenotype CD133 positive and CD44 positive.J. Cell. Physiol. 228: 408-415, 2013. ß 2012 Colon cancer is the second leading cause of cancer-related death. The majority of these deaths are due to metastasis, with the liver easily the most common site of deposit (LeGolvan and Resnick, 2010). Combining surgery and chemotherapy in the treatment of patients with colon hepatic metastases is increasingly becoming the standard of care. However, controversy remains regarding the juxtapositioning of chemotherapy and surgery, the duration of chemotherapy, and particularly, the use of preoperative chemotherapy in the treatment of patients with initially resectable metastases (Nordlinger et al., 2010).Cancer metastasis has been explained by at least two models: a progression model and an initiating model. In the former, metastatic capacity is acquired during cancer progression in a subpopulation of cells through sequential genetic mutations or epigenetic alterations (Gray, 2010), in genes associated with proteolysis of local extracellular matrix attachments (Nagashima et al., 1997), adhesive alterations (Furger et al., 2001), angiogenesis (Weber, 2008), viable vascular dissemination, distant embolization, and survival in a new environment (Folkman, 1990;Hynes, 2003;Bird et al., 2006). However, not all of these genetic alterations occur during the process of liver metastasis (Gray, 2010). In the initiation model, cells with metastatic potential are determined by early mutational events in a progenitor cell, named cancer stem cell (CSCs) or tumor-initiating cells (TIC; Clarke and Fuller, 2006;Polyak and Hahn, 2006;Odoux et al., 2008), even if few data support the hypothesis of its role in the colon metastatic process in humans (Horst et al., 2009b;Puglisi et al., 2009;Ju e...

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“…Serial transplantations have revealed significant genetic instability in tumors originating from CSCs (39,71,72). One clear manifestation of this phenomenon is that tumors become more aggressive with in vivo passaging, with earlier tumor presentation and faster tumor growth rates (11,40,71,72).…”

Section: Inconsistencies Of the Csc Hypothesismentioning

confidence: 99%

Die hard: Are cancer stem cells the Bruce Willises of tumor biology?

et al. 2008

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In recent years, an exponentially growing number of studies have focused on identifying cancer stem cells (CSC) in human malignancies. The rare CSCs could be crucial in controlling and curing cancer: through asymmetric division CSCs supposedly drive tumor growth and evade therapy with the help of traits shared with normal stem cells such as quiescence, self-renewal ability, and multidrug resistance pump activity. Here, we give a brief overview of techniques used to confirm the stem cell-like behavior of putative CSCs and discuss markers and methods for identifying, isolating, and culturing them. We touch on the limitations of each marker and why the combined use of CSC markers, in vitro and in vivo assays may still fail to identify all relevant CSC populations. Finally, the various experimental findings supporting and contradicting the CSC hypothesis are summarized. The large number of tumor types thus far with a subpopulation of uniquely tumorigenic and therapy resistant cells suggests that despite the unanswered questions and inconsistencies, the CSC hypothesis has a legitimate role to play in tumor biology. At the same time, experimental evidence supporting the established alternative theory of clonal evolution can be found as well. Therefore, a model that describes cancer initiation and progression should combine elements of clonal evolution and CSC theory. '

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A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer

Cited by 152 publications

References 44 publications

Understanding cancer stem cell heterogeneity and plasticity

Understanding cancer stem cell heterogeneity and plasticity

Co‐expression of CD133⁺/CD44⁺ in human colon cancer and liver metastasis

Die hard: Are cancer stem cells the Bruce Willises of tumor biology?

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A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer

Cited by 152 publications

References 44 publications

Understanding cancer stem cell heterogeneity and plasticity

Understanding cancer stem cell heterogeneity and plasticity

Co‐expression of CD133+/CD44+ in human colon cancer and liver metastasis

Die hard: Are cancer stem cells the Bruce Willises of tumor biology?

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Co‐expression of CD133⁺/CD44⁺ in human colon cancer and liver metastasis