Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

Guzhova, Irina V.; Hultquist, Anne; Cetinkaya, Cihan; Nilsson, Kenneth; Påhlman, Sven; Larsson, Lars‐Gunnar

doi:10.1002/ijc.1443

Cited by 26 publications

(23 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1D (top). This is in agreement with previous reports on MYCN mRNA expression in LA-N-5 cells (22,23). In contrast, only a slight reduction in MYCN mRNA expression was observed in IMR-32 cells in response to RA+IFN-g treatment ( Fig.…”

Section: Resultssupporting

confidence: 93%

“…S1). 6 Supplementary Table S1 6 shows that IFN-g enhanced RAinduced differentiation measured as the percentage of morphologically differentiated cells with neurites as reported previously (23). Furthermore, in contrast to the effect of each agent alone, complete growth arrest rather than only growth retardation was induced by their combination (data not shown; Supplementary Table S1; 6 ref.…”

Section: Resultssupporting

confidence: 68%

“…Furthermore, in contrast to the effect of each agent alone, complete growth arrest rather than only growth retardation was induced by their combination (data not shown; Supplementary Table S1; 6 ref. 23).…”

Section: Resultsmentioning

confidence: 99%

“…Northern blot analysis was carried out as described (23). For MAD1, a 1.1-kb NotI/EcoRI fragment from the cDNA clone pVZ1mad (kindly provided by D. Ayer) was used, whereas for MAX, a 540-bp EcoRI fragment from the MAX cDNA clone pVZ1max (kindly provided by R. Eisenman) was used.…”

Section: Cell Cultures and Induction Of Differentiationmentioning

confidence: 99%

“…For MAD1, a 1.1-kb NotI/EcoRI fragment from the cDNA clone pVZ1mad (kindly provided by D. Ayer) was used, whereas for MAX, a 540-bp EcoRI fragment from the MAX cDNA clone pVZ1max (kindly provided by R. Eisenman) was used. The probes for MYCN and GAPDH have been described (23).…”

Section: Cell Cultures and Induction Of Differentiationmentioning

confidence: 99%

See 4 more Smart Citations

Combined IFN-γ and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells

Cetinkaya

Hultquist

et al. 2007

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

The MYCN protooncogene is involved in the control of cell proliferation, differentiation, and survival of neuroblasts. Deregulation of MYCN by gene amplification contributes to neuroblastoma development and is strongly correlated to advanced disease and poor outcome, emphasizing the urge for new therapeutic strategies targeting MYCN function. The transcription factor N-Myc, encoded by MYCN, regulates numerous genes together with its partner Max, which also functions as a cofactor for the Mad/Mnt family of Myc antagonists/transcriptional repressors. We and others have previously reported that IFN-; synergistically potentiates retinoic acid (RA) -induced sympathetic differentiation and growth inhibition in neuroblastoma cells. This study shows that combined treatment of MYCN-amplified neuroblastoma cells with RA+IFN-; down-regulates N-Myc protein expression through increased protein turnover, up-regulates Mad1 mRNA and protein, and reduces N-Myc/Max heterodimerization. This results in a shift of occupancy at the ornithine decarboxylase N-Myc/Mad1 target promoter in vivo from N-Myc/Max to Mad1/Max predominance, correlating with histone H4 deacetylation, indicative of a chromatin structure typical of a transcriptionally repressed state. This is further supported by data showing that RA+IFN-; treatment strongly represses expression of N-Myc/Mad1 target genes ornithine decarboxylase and hTERT. Our results suggest that combined IFN-; and RA signaling can form a basis for new therapeutic strategies targeting N-Myc function for patients with high-risk, MYCN-amplified neuroblastoma. [Mol Cancer Ther 2007;6(10):2634 -41]

show abstract

Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Cell Cultures and Induction Of Differentiationmentioning

confidence: 99%

Section: Cell Cultures and Induction Of Differentiationmentioning

confidence: 99%

See 3 more Smart Citations

Combined IFN-γ and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells

Cetinkaya

Hultquist

et al. 2007

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

Viability and differentiation of neural precursors on hyaluronic acid hydrogel scaffold

Pan

Ren

Cui

et al. 2009

J of Neuroscience Research

View full text Add to dashboard Cite

The traditional notion that injured neurons are unable to regenerate in the adult mammalian brain and spinal cord has long been a concern. This view has led to methodology designed to overcome this problem, most recently by advancements in tissue engineering. Here, neural precursor cells (NPCs) and the Nogo receptor antibody (NgR-Ab) or poly-L-lysine (PLL) were tested in concert with hyaluronic acid hydrogel scaffolds (HA). In particular, we wished to optimize viability and differentiation of NPCs within HA hydrogel scaffolds. Our results show that HA hydrogels can be modified physically or chemically to improve NPCs attachment on the scaffolding doped with NgR-Ab or PLL. Both the HA hydrogels and their modifications support the viability of NPCs. NPCs were also able to differentiate into neurons and glial cells on HA hydrogels, although this was affected by the different modifications. Immunofluorescence showed that fewer beta-III-tubulin antibody and antineurofilament antibody-positive cells were found on HA-PLL hydrogel compared with HA or HA NgR-Ab hydrogels. This indicates that the PLL-modified HA hydrogels may inhibit differentiation of NPCs, whereas modification by NgR-Ab had no such effect. Finally, the NgR-Ab-modified HA scaffold can be used as not only a NPC delivery system but also a bioactive factor transportation system for CNS repair.

show abstract

Soluble factors released by activated cytotoxic T lymphocytes interfere with death receptor pathways in neuroblastoma

Geer

Carlson

Kogner³

et al. 2007

Cancer Immunol Immunother

View full text Add to dashboard Cite

Neuroblastoma (NB) is often described as an unfavorable target for both HLA-restricted and death receptor-mediated elimination by cytotoxic T lymphocytes (CTLs) due to low or absent HLA class I and caspase-8 expression. We investigated the effects of soluble factors released by CTLs activated by TCR triggering (named as activated supernatant; AS) on the levels and composition of cell surface molecules involved in HLA-restricted and HLA-independent NB cell recognition (surface immune phenotype). Using a panel of long-term propagated NB cell lines and freshly isolated primary human NB cells, we analyzed surface expression of the (1) cognate receptors for TNFalpha, Fas and TRAIL; (2) HLA class I and II heterodimers; (3) adhesion molecules; (4) the intracellular expression and activation of caspase-8, as well as (5) the susceptibility of NB cells to death receptor-mediated killing prior to and after exposure to AS. The exposure of NB cells to soluble factors released by activated CTLs skewed the surface immune phenotype of both long term cultured and primary NB cells, induced the expression and activation of caspase-8 and increased the susceptibility of tumor cells to lysis by TRAIL and Fas-agonistic antibody. Blocking experiments identified IFNgamma and TNFalpha as main factors responsible for modulating the surface antigens of NB cells by AS. Our data suggest that recruitment of CTLs activated on third party targets into the vicinity of the NB tumor mass, may override the "silent" immune phenotype of NB cells via the action of soluble factors.

show abstract

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

Cited by 26 publications

References 48 publications

Combined IFN-γ and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells

Combined IFN-γ and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells

Viability and differentiation of neural precursors on hyaluronic acid hydrogel scaffold

Soluble factors released by activated cytotoxic T lymphocytes interfere with death receptor pathways in neuroblastoma

Contact Info

Product

Resources

About