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Neuronal characteristics of small-cell lung cancer.

Onganer PU, Seckl MJ, Djamgoz MB - Br. J. Cancer (2005)

Bottom Line: This review outlines and discusses these characteristics in the light of recent developments in the field.Emphasis is placed upon neuronal cell adhesion molecules, neurone-restrictive silencer factor, neurotransmitters/peptides and voltage-gated ion, especially Na(+) channels.The hypothesis is put forward that acquisition of such characteristics and the membrane 'excitability' that would follow can accelerate metastatic progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, UK.

ABSTRACT
Wide ranging experimental evidence suggests that human small-cell lung cancer (SCLC) has a number of molecular and subcellular characteristics normally associated with neurones. This review outlines and discusses these characteristics in the light of recent developments in the field. Emphasis is placed upon neuronal cell adhesion molecules, neurone-restrictive silencer factor, neurotransmitters/peptides and voltage-gated ion, especially Na(+) channels. The hypothesis is put forward that acquisition of such characteristics and the membrane 'excitability' that would follow can accelerate metastatic progression. The clinical potential of the neuronal characteristics of SCLC, in particular ion channel expression/activity, is discussed in relation to possible novel diagnostic and therapeutic modalities.

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Related in: MedlinePlus

Immunohistochemical localisation of voltage-gated Na+ channel (VGSC) protein expression in human lung tissues, using a commercial pan-VGSC antibody. (A and B) SCLC, (C and D), normal lung epithelia. Voltage-gated Na+ channel immunoreactivity showed marked upregulation in SCLC (B vs D). Left hand panels (A and C) represent phase contrast images, right hand panels (B and D) are bright field images. Scale bar, 15 μm, applicable to all parts of the figure.
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fig2: Immunohistochemical localisation of voltage-gated Na+ channel (VGSC) protein expression in human lung tissues, using a commercial pan-VGSC antibody. (A and B) SCLC, (C and D), normal lung epithelia. Voltage-gated Na+ channel immunoreactivity showed marked upregulation in SCLC (B vs D). Left hand panels (A and C) represent phase contrast images, right hand panels (B and D) are bright field images. Scale bar, 15 μm, applicable to all parts of the figure.

Mentions: The possible involvement of VGSC activity in metastatic behaviour of human SCLC cells has recently been investigated by determining their role in endocytic membrane activity, a measure of vesicular secretion and plasma membrane protein turnover (Onganer and Djamgoz, 2005) and proliferation (Onganer et al, 2004). A variety of human SCLC cell lines (H69, H209 and H510) and a normal human airway epithelial (16HBE14o) cell line were used. Endocytic uptake of a noncytotoxic tracer, horseradish peroxidase (HRP) into SCLC cells was vesicular and was inhibited significantly by TTX, as well as clinically used VGSC drugs, lidocaine and phenytoin (Figure 1D). These effects were dose dependent. None of the VGSC blockers used had any effect on tracer uptake into the 16HBE14o cells (Onganer and Djamgoz, 2005). Treatment with TTX for 24 h caused ∼60% significant reduction in proliferation of SCLC but only ∼15% in normal airway epithelial cells (Onganer et al, 2004). These data would suggest strongly that VGSC upregulation could enhance metastatic cell behaviour in SCLC, as shown previously for prostate and breast cancer. Voltage-gated Na+ channel protein expression in human clinical biopsies of SCLC was studied by immunohistochemical staining using a pan-VGSC antibody. There was little or no VGSC protein expressed in normal human lung tissues (Figure 2C and D). On the other hand, significant upregulation of VGSC protein was seen in SCLC (Figure 2A and B) (Onganer et al, 2004).


Neuronal characteristics of small-cell lung cancer.

Onganer PU, Seckl MJ, Djamgoz MB - Br. J. Cancer (2005)

Immunohistochemical localisation of voltage-gated Na+ channel (VGSC) protein expression in human lung tissues, using a commercial pan-VGSC antibody. (A and B) SCLC, (C and D), normal lung epithelia. Voltage-gated Na+ channel immunoreactivity showed marked upregulation in SCLC (B vs D). Left hand panels (A and C) represent phase contrast images, right hand panels (B and D) are bright field images. Scale bar, 15 μm, applicable to all parts of the figure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361510&req=5

fig2: Immunohistochemical localisation of voltage-gated Na+ channel (VGSC) protein expression in human lung tissues, using a commercial pan-VGSC antibody. (A and B) SCLC, (C and D), normal lung epithelia. Voltage-gated Na+ channel immunoreactivity showed marked upregulation in SCLC (B vs D). Left hand panels (A and C) represent phase contrast images, right hand panels (B and D) are bright field images. Scale bar, 15 μm, applicable to all parts of the figure.
Mentions: The possible involvement of VGSC activity in metastatic behaviour of human SCLC cells has recently been investigated by determining their role in endocytic membrane activity, a measure of vesicular secretion and plasma membrane protein turnover (Onganer and Djamgoz, 2005) and proliferation (Onganer et al, 2004). A variety of human SCLC cell lines (H69, H209 and H510) and a normal human airway epithelial (16HBE14o) cell line were used. Endocytic uptake of a noncytotoxic tracer, horseradish peroxidase (HRP) into SCLC cells was vesicular and was inhibited significantly by TTX, as well as clinically used VGSC drugs, lidocaine and phenytoin (Figure 1D). These effects were dose dependent. None of the VGSC blockers used had any effect on tracer uptake into the 16HBE14o cells (Onganer and Djamgoz, 2005). Treatment with TTX for 24 h caused ∼60% significant reduction in proliferation of SCLC but only ∼15% in normal airway epithelial cells (Onganer et al, 2004). These data would suggest strongly that VGSC upregulation could enhance metastatic cell behaviour in SCLC, as shown previously for prostate and breast cancer. Voltage-gated Na+ channel protein expression in human clinical biopsies of SCLC was studied by immunohistochemical staining using a pan-VGSC antibody. There was little or no VGSC protein expressed in normal human lung tissues (Figure 2C and D). On the other hand, significant upregulation of VGSC protein was seen in SCLC (Figure 2A and B) (Onganer et al, 2004).

Bottom Line: This review outlines and discusses these characteristics in the light of recent developments in the field.Emphasis is placed upon neuronal cell adhesion molecules, neurone-restrictive silencer factor, neurotransmitters/peptides and voltage-gated ion, especially Na(+) channels.The hypothesis is put forward that acquisition of such characteristics and the membrane 'excitability' that would follow can accelerate metastatic progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, UK.

ABSTRACT
Wide ranging experimental evidence suggests that human small-cell lung cancer (SCLC) has a number of molecular and subcellular characteristics normally associated with neurones. This review outlines and discusses these characteristics in the light of recent developments in the field. Emphasis is placed upon neuronal cell adhesion molecules, neurone-restrictive silencer factor, neurotransmitters/peptides and voltage-gated ion, especially Na(+) channels. The hypothesis is put forward that acquisition of such characteristics and the membrane 'excitability' that would follow can accelerate metastatic progression. The clinical potential of the neuronal characteristics of SCLC, in particular ion channel expression/activity, is discussed in relation to possible novel diagnostic and therapeutic modalities.

Show MeSH
Related in: MedlinePlus