Brain cancer propagating cells: biology, genetics and targeted therapies - PubMed (original) (raw)

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Brain cancer propagating cells: biology, genetics and targeted therapies

Costas G Hadjipanayis et al. Trends Mol Med. 2009 Nov.

Abstract

Cancer propagating cells (CPCs) within primary central nervous system (CNS) tumors (glioblastoma multiforme (GBM), medulloblastoma (MB) and ependymoma) might be integral to tumor development and perpetuation. These cells, also known as brain cancer propagating cells (BCPCs), have the ability to self-renew and proliferate. BCPCs can initiate new tumors in mice with high efficiency and these exhibit many features that are characteristic of patient's brain tumors. Accumulating evidence suggests that BCPCs might originate from the transformation of neural stem cells (NSCs) and their progenitors. Furthermore, recent studies have shown that NSC surface markers also define BCPCs. Ultimately, treatments that include specific targeting of BCPCs might potentially be more effective at treating the entire tumor mass, translating to improved patient survival and quality of life.

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Figures

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Photographs courtesy of D. Brat and C. Tucker-Burden.

Figure 1

Figure 1

Brain tumors. Location of GBM, MB and ependymoma tumors in the CNS.

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Figure 2

Normal CNS differentiation and transformation for CNS tumor formation. NSCs can differentiate into neural and glial progenitors. Neural progenitors differentiate into neurons, whereas glial progenitors are committed to oligodendrocytes, ependymal cells or astrocytes. CNS tumor formation might originate from the transformation of NSCs into BCPCs. Glial progenitors might transform into brain tumor progenitor-like cells that could engender CNS tumors (GBMs, MBs and ependymomas). The transformation of neurons, oligodendrocytes, ependymal cells and astrocytes has traditionally been thought to form CNS tumors. BCPCs can differentiate into brain tumor progenitor-like cells or more differentiated progeny, which can lead to CNS tumor formation. Stromal cells, either from the local brain microenvironment or recruited systemically, can be essential for tumor maintenance, progression and recurrence.

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Figure 3

Human neurospheres cultured from glioblastoma tumor. The figure shows different magnifications of cultured neurospheres (4×, 20× and 40×).

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Figure 4

Human glioblastoma xenograft generated in an athymic nu/nu mouse eight weeks after the intracranial implantation of neurospheres harvested from a resected glioblastoma specimen. a) T2-weighted MRI of mouse brain showing xenograft (marked by *). b) Hematoxylin/eosin stained section of mouse brain showing xenograft (marked by arrow). c) Hematoxylin/eosin stained section of mouse brain demonstrating the invasion of human glioblastoma xenograft into surrounding brain (marked by arrows).

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