Written in English
Most current research on human brain tumours is focused on the molecular and cellular analysis of the bulk tumour mass. However, there is overwhelming evidence in some malignancies that the tumour clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumour clone is organized as a hierarchy that originates from rare leukemic stem cells. Therefore, the cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells that have stem cell properties. Although the existence of CSC in human leukemia is established, except for breast cancer, there is little direct evidence for CSC in solid tumours.We prospectively identified and purified a subpopulation of tumour cells from a variety of human brain tumours that exhibited the stem cell properties of proliferation, self-renewal, and differentiation in vitro. The brain tumour stem cell (BTSC) was exclusively isolated with the cell fraction expressing the neural precursor cell surface marker CD133. CD133 was expressed in a minority of brain tumour cells, and ranged from 0.1 to 30% in tumours of varying phenotype. The increased self-renewal capacity of the in vitro BTSC was highest from the most aggressive clinical samples of medulloblastoma and glioblastoma compared with low-grade gliomas. Conversely, CD133- cells showed no in vitro self-renewal capacity and very limited proliferative ability. The CD133+ cells could also differentiate in culture into tumour cells that phenotypically resembled the tumour from the patient.In order to test the capacity of the in vitro BTSC to initiate tumours in vivo, we used a xenograft assay to identify human brain tumour initiating cells (BTIC). Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that was serially transplantable and was a phenocopy of the patient"s original tumour, whereas injection of 105 CD133- cells engrafted but did not cause a tumour. Therefore, CD133+ brain tumour cells satisfy the definition of cancer stem cells in that they are able to generate a replica of the patient"s tumour and they exhibit self-renewal ability in vivo through serial retransplantation. The identification of a brain tumour initiating cell provides new insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a novel cellular target for more effective cancer therapies.
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These cells have been termed brain tumour stem cells (BTSCs) or brain tumour initiating cells (BTICs), and they are responsible for tumour initiation and chemo/radiation therapy resistance in primary brain tumours. A hematopoietic stem cell marker, CD (prominin 1), has been proposed to be a BTIC marker,,,.Cited by: cancer stem cell invasion R ecent improvements in cell purification and transplantation techniques have contributed to the identification of cell pop-ulations known as tumor-initiating cells (T-ICs). These findings led to the idea that tumors are organized as hierarchies of cells sustained by such T-ICs, conceptually termed cancer stem cellsCited by: of brain tumour development and growth in terms of stem cell biology. The cancer stem cell hypothesis states that tumours are initiated and maintained by a (typically small) subset of cancer cells in possession of certain deﬁning properties of stem cells – namely, the abilities to self-renew and to. Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (T-ICs). These findings led to the idea that tumors are organized as hierarchies of cells sustained by such T-ICs, conceptually termed cancer stem cells (CSCs) (1, 2).
Brain tumour initiating cell culture Two previously characterized GBM patient-derived BTIC lines, BT and BT (Cusulin et al., ; Kelly et al., ; Verginelli et al., ) were used. Given the identification of CD + tumour-initiating cells from human colon cancer, published last month 8,9, it would seem that these approaches are ripe for testing in other human cancers. Cancer stem cells. A solid tumor is a heterogeneous mass made up of a variety of cell types, including cancer cells, cells in the tumor microenvironment and the extracellular matrix. CSC make up a small subpopulation of the cancer cells that are thought to play a major role in tumor initiation and progression. Major clinical issues in bladder cancer include the identification of prediction markers and novel therapeutic targets for invasive bladder cancer. In the current study, we describe the isolation and characterization of a tumor-initiating cell (T-IC) subpopulation in primary human bladder cancer, based on the expression of markers similar to that of normal bladder basal cells (Lineage-CD44+CK5.
The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown. Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess. cycling stem cell-like cells that harbour tumour-initiating potential. Cancer stem cells are generally thought to be resistant to treatment, yet retain the ability to reconstitute the varied cell types within the heterogeneous tumour mass once treatment ceases. Brain tumours were among the first cancers in which stem cell-like cells were. 2. Brain tumors as stem cell problems. Human brain tumors, on the heels of work in human breast cancer (Al-Hajj et al., ), were among the first solid tumors in which a cellular hierarchy for tumor initiation, utilizing prospective cell sorting and limit dilution analysis in vivo, was demonstrated (Singh et al., ).