Angiogenesis-independent tumor growth mediated by stem-like cancer cells

Sakariassen, Per Øystein; Prestegarden, Lars; Wang, Jian; Skaftnesmo, Kai-Ove; Mahesparan, Rupavathana; Molthoff, Carla F. M.; Sminia, Peter; Sundlisæter, Eirik; Misra, Ankita; Tysnes, Berit Bølge; Chekenya, Martha; Peters, H.; Lende, Gabriel; Kalland, Karl H.; Øyan, Anne Margrete; Petersen, Kjell; Jonassen, Inge; Kogel, Albert van der; Feuerstein, Burt G.; Terzis, A. J. A.; Bjerkvig, Rolf; Enger, Per Øyvind

doi:10.1073/pnas.0607668103

Cited by 200 publications

(246 citation statements)

References 56 publications

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“…11,43 However, most glioma cell lines and primary glioma spheroids are easily propagated in serum-containing medium, and they are still tumorgenic in vivo when xenografted into animals. [24][25][26]44 In fact, a recent study reported that most of the cells in the C6 rat glioma cell line, exhibited cancer stem cell properties, regardless of whether they were CD133 positive or CD133 negative. 22 Thus, the ability of selfrenewal may not be exclusive to glioma cells expressing the CD133 marker but instead shared by many tumor phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…The 1st generation tumors did not exhibit contrast enhancement indicating intact vessel structures as previously described. 24,25 As in the patients, the addition of a contrast agent revealed a hyper-intense area in the high generation tumors indicating a compromised blood-brain-barrier (BBB) (Fig. 1b).…”

Section: Cd133 Expression Coincides With Onset Of Tumor Angiogenesismentioning

confidence: 99%

“…24 The establishment of naive human GBM biopsy material into a host of a different species (rat), and the expression of primitive cell markers, indicate a high cellular adaptability. In the present work, we used this model to assess the expression of CD133 in GBM patient biopsies as well as in the xenograft tumors during passaging.…”

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confidence: 99%

“…22 Furthermore, it has recently been demonstrated that CD133 negative cells from human glioblastoma multiforme (GBM) exhibit cancer stem cell properties as well, although their proliferation index was lower than for CD133 positive cells. 23 Thus, the role of CD133 positive cells versus other cell populations in brain tumor initiation and progression is still uncertain.We have previously developed a human glioma model by implanting human GBM biopsy spheroids into the brains of nude rats, 24,25 and showed that these tumors express a number of stem cell markers. 24 The establishment of naive human GBM biopsy material into a host of a different species (rat), and the expression of primitive cell markers, indicate a high cellular adaptability.…”

mentioning

confidence: 99%

“…We have previously developed a human glioma model by implanting human GBM biopsy spheroids into the brains of nude rats, 24,25 and showed that these tumors express a number of stem cell markers. 24 The establishment of naive human GBM biopsy material into a host of a different species (rat), and the expression of primitive cell markers, indicate a high cellular adaptability.…”

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confidence: 99%

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CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells

Wang

Sakariassen

Tsinkalovsky

et al. 2007

Intl Journal of Cancer

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CD133 is a cell surface marker expressed on progenitors of haematopoietic and endothelial cell lineages. Moreover, several studies have identified CD133 as a marker of brain tumor-initiating cells. In this study, human glioblastoma multiforme biopsies were engrafted intracerebrally into nude rats. The resulting tumors were serially passaged in vivo, and monitored by magnetic resonance imaging. CD133 expression was analyzed at various passages. Tumors initiated directly from the biopsies expressed little or no CD133, and showed no contrast enhancement suggesting an intact blood-brain barrier. During passaging, the tumors gradually displayed more contrast enhancement, increased angiogenesis and a shorter survival. Real-time qPCR and immunoblots showed that this was accompanied by increased CD133 expression. Primary biopsy spheroids and xenograft tumors were subsequently dissociated and flow sorted into CD133 negative and CD133 positive cell populations. Both populations incorporated BrdU in cell culture, and expressed the neural precursor marker nestin. Notably, CD133 negative cells derived from 6 different patients were tumorgenic when implanted into the rat brains. For 3 of these patients, analysis showed that the resulting tumors contained CD133 positive cells. In conclusion, we show that CD133 negative glioma cells are tumorgenic in nude rats, and that CD133 positive cells can be obtained from these tumors. Upon passaging of the tumors in vivo, CD133 expression is upregulated, coinciding with the onset of angiogenesis and a shorter survival. Thus, our findings do not suggest that CD133 expression is required for brain tumor initiation, but that it may be involved during brain tumor progression. ' 2007 Wiley-Liss, Inc.Key words: CD133; brain cancer; angiogenesis; cancer stem cell; xenograft At present, there is a search for tumor cell subpopulations that may be responsible for tumor initiation and progression. Such cells have been termed cancer stem cells and are defined by their capacity to self-renew, express stem cell markers and to initiate tumors in vivo. 1,2 Potential cancer stem cells have been identified in leukaemias, 3-5 breast, 6 prostate, 7 bone, 8 colon and brain cancer. [9][10][11][12][13] In some cases, these tumor-initiating cells have been distinguished from the non-tumor-initiating ones based on expression of cell surface markers. For instance, it has been shown that only CD44 1 / CD24 2 /Lineage 2 breast cancer cells are tumorgenic in animals. 6 In malignant brain tumors, CD133 has been suggested to be a cancer stem cell marker 11,14 since only CD133 positive cells from brain tumor biopsy material were able to initiate brain cancer in a mouse model. 14 Prominin-1 (PROM-1), also called CD133, is a protein with several isoforms of unknown physiological or pathological function, and is localized both in the cytoplasm and at the cell surface. 15,16 It is expressed by human neural stem cells and has been proposed to have a function in central nervous system (CNS) development. 17 It is also express...

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Section: Discussionmentioning

confidence: 99%

Section: Cd133 Expression Coincides With Onset Of Tumor Angiogenesismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells

Wang

Sakariassen

Tsinkalovsky

et al. 2007

Intl Journal of Cancer

Self Cite

507

393

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CNSCancers

Graeme

2010

Burger's Medicinal Chemistry and Drug Discovery

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CNS tumors represent a diverse collection of tumor types driven by a range of signaling inputs that often generate highly aggressive and at the same time heterogeneous tumor types. The effect of these tumors is particularly dramatic and impacts on children as well as adults. Malignant CNS tumors are characterized by being highly heterogeneous, aggressive, and frequently invasive, leading to poor overall patient survival times. As CNS tumors present within the nervous system, there are particular challenges in the development of effective molecular‐targeted therapies in dealing not only with the aggressive nature of these tumors and their ability to evade treatment but also, particularly, with maintaining normal neuronal and brain functions. Compounding this is the need to deliver systemically small molecules or other agents such as vaccines and for immunotherapy approaches to confront the complexity of the relationship between the nervous system and the immune system. Research to find effective treatments for CNS tumors is being facilitated by two key inputs both of which are reviewed in this chapter; first, a much greater understanding of tumor pathobiology and the potential role of developmental signaling pathways and tumor stem‐like cells, and by the development of animal models that more adequately represent endpoints measurable in the clinic. Together, these advances should assist in the selection of better targets and the optimization of better compounds to progress into clinical trials.

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Modeling the effect of chemotaxis on glioblastoma tumor progression

et al. 2011

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Tumor progression depends on the intricate interplay between biological processes that span the molecular and macroscopic scales. A mathematical agent-based model is presented to describe the 3-D (three-dimensional) progression of a brain tumor type (i.e., glioblastoma multiforme) as the collective behavior of individual tumor cells whose fate is determined by intracellular signaling pathways (i.e., MAPK pathway) that are governed by the temporal-spatial distribution of key biochemical cues (i.e., growth factors, nutrients). The model is used to investigate how tumor growth and invasiveness depend on the response of migrating tumor cells to chemoattractants. Simulation results suggest that individual cell sensitivity to chemical gradients is necessary to generate in silico tumors with the irregular shape and diffusive tumor-stroma interface characteristic of glioblastomas. In addition, vascular network damage influences tumor growth and invasiveness. The results quantitatively recapitulate the central role that nutrient availability and signaling proteins have on tumor invasive properties.

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Angiogenesis-independent tumor growth mediated by stem-like cancer cells

Cited by 200 publications

References 56 publications

CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells

CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells

CNSCancers

Modeling the effect of chemotaxis on glioblastoma tumor progression

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