Surface Alloantigens of Plasma Cells

Takahashi, Toshitada; Old, Lloyd J.; Boyse, Edward A.

doi:10.1084/jem.131.6.1325

Cited by 260 publications

(107 citation statements)

References 17 publications

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“…17 This membrane-bound enzyme has broad substrate specificity cleaving phosphodiester, pyrophosphate and phosphosulphate bonds of nucleotides and nucleotide derivatives. 26,32 Originally, E-NPP1 was discovered on the surface of mouse B-lymphocytes 33 and is expressed in a large variety of human tissues including brain. 26 Here we describe an elevated ENPP1 expression in GSCs compared with normal brain extracts and fNSCs.…”

Section: Discussionmentioning

confidence: 99%

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

et al. 2014

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Glioblastomas are highly aggressive brain tumours and are characterised by substantial cellular heterogeneity within a single tumour. A sub-population of glioblastoma stem-like cells (GSCs) that shares properties with neural precursor cells has been described, exhibiting resistance to therapy and therefore being considered responsible for the high recurrence rate in glioblastoma. To elucidate the underlying cellular processes we investigated the role of phosphatases in the GSC phenotype, using an in vitro phosphatome-wide RNA interference screen. We identified a set of genes, the knockdown of which induces a significant decrease in the glioma stem cell marker CD133, indicating a role in the glioblastoma stem-like phenotype. Among these genes, the ecto-nucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) was found to be highly expressed in GSCs compared with normal brain and neural stem cells. Knockdown of ENPP1 in cultured GSCs resulted in an overall downregulation of stem cell-associated genes, induction of differentiation into astrocytic cell lineage, impairment of sphere formation, in addition to increased cell death, accumulation of cells in G1/G0 cell cycle phase and sensitisation to chemotherapeutic treatment. Genome-wide gene expression analysis and nucleoside and nucleotide profiling revealed that knockdown of ENPP1 affects purine and pyrimidine metabolism, suggesting a link between ENPP1 expression and a balanced nucleoside-nucleotide pool in GSCs. The phenotypic changes in E-NPP1-deficient GSCs are assumed to be a consequence of decreased transcriptional function of E2F1. Together, these results reveal that E-NPP1, by acting upstream of E2F1, is indispensable for the maintenance of GSCs in vitro and hence required to keep GSCs in an undifferentiated, proliferative state. Glioblastoma, classified by the WHO (World Health Organization) as grade IV astrocytoma, 1 is the most common primary malignant brain tumour in adults. Despite progress in surgical resection, radiation and chemotherapy, glioblastoma remains a deadly disease with a median survival time of about 1 year. 2 One particular therapeutic challenge for glioblastoma treatment is posed by their remarkable intratumoural cellular heterogeneity. Several studies indicate the existence of a highly tumourigenic, sub-population of cancer cells with stemlike characteristics. [3][4][5] There is substantial evidence that these so-called cancer stem cells have inherent chemotherapy and radiation resistance. 6,7 These findings suggest that cancer cells harbouring stem cell-like characteristics are responsible for ineffective therapy, explaining high recurrence rates despite significant reduction in tumour volume. Glioblastoma stem-like cells (GSCs) share properties with neural precursor cells, such as a capacity for self-renewal, differentiation and maintained proliferation, as well as stem cell marker expression. 4,5,8,9 GSCs were originally defined by expression of CD133 (Prominin-1) and its extracellular AC133 epitope. 4 Although recent...

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Section: Discussionmentioning

confidence: 99%

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

et al. 2014

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“…The tumour was transmitted to the newborn mice by s.c. inoculations in the neck region of 3 x 104 live cells, obtained by mechanical teasing, in 0-1 ml volume. Cell viability was determined by the trypan blue dye exclusion test as described by Takahashi, Old and Boyse (1970). Mice were periodically examined for a period of 80 days to determine the day of tumour appearance.…”

Section: Methodsmentioning

confidence: 99%

Induction of resistance or enhancement to a transplantable murine plasmacytoma by transfer of non-immune leucocytes

Giovarelli¹,

Comoglio

Forni³

1976

Br J Cancer

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Newborn mice have a lower spontaneous resistance to the growth of a syngeneic plasmacytoma (MOPC-460) as compared to adult mice. The transfer of different leucocyte populations from non-immunized adult donors to newborn mice influence in a dual way the resistance to MOPC-460 growth, depending on the number of cells transferred. The transfer of a low number of neutrophils, thymus or spleen cells enhances the MOPC-460 takes. Higher numbers of neutrophils, thymus or bone marrow cells induce an effective protenction. By contrast, macrophages over a dose of 1 X 10(4) constantly produce a reduction of tumour growth.

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“…A secretory plasmocytoma IgA (MOPC-460), which was chemically induced in the N.I.H. Balb/c strain (Potter, 1967), and an adenocarcinoma (ADK-lt) by the exclusion of Trypan blue under the conditions described by Takahashi, Old and Boyse (1970). The animals with palpable tumours were sacrificed at intervals of 20 days and the tumours excised and weighed.…”

Section: Methodsmentioning

confidence: 99%

Growth of Syngeneic Tumours in Unimmunized Newborn and Adult Hosts

Forni¹,

Comoglio

1973

Br J Cancer

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Summary.-The post-natal development of " natural " resistance of Balb/c mice to the challenge of syngeneic tumours was studied using injections of various doses of live neoplastic cells into untreated animals of increasing age, from neonatal to 12 weeks.The minimum quantity of neoplastic cells capable of inducing tumours increased in parallel with the age of the animals. Immunodepression with whole body irradiation with X-rays reduced the resistance offered by adult mice to tumour challenge to that of the neonate. The relationship of the increase in resistance to tumour challenge with the development of the animals' own immune response during the course of post-natal growth is discussed.

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Surface Alloantigens of Plasma Cells

Cited by 260 publications

References 17 publications

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

Induction of resistance or enhancement to a transplantable murine plasmacytoma by transfer of non-immune leucocytes

Growth of Syngeneic Tumours in Unimmunized Newborn and Adult Hosts

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