Limits...
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.

Show MeSH

Related in: MedlinePlus

Whole-cell patch-clamp recordings from SCLC H146 cells showing expression voltage activated inward (Na+) currents. (A) A family of membrane currents activated at different membrane potentials (values in mV indicated on the right). (B) Current–voltage relationship of voltage-gated Na+ currents. Circles – normal data; triangles – effect of 100 nM TTX; squares – effect of Na+-free medium (choline+ used as substitute). (C) Dose–response curve for TTX-induced suppression of the Na+ current, I (%) expressed as a percentage of the control value. (A–C) Modified from Blandino et al (1995). (D) Effects of 100 nM TTX (1), 200 nM lidocaine (2) and 200 nM phenytoin (3) on endocytic membrane activity (HRP uptake) into the SCLC cell line, H510 (left-hand sets of histobars) and the normal airway epithelial cell line, 16HBE14o (right-hand sets of histobars). OD540, optical density of HRP content of cell lysates. Each data set of three histobars shows the effects of the following: HRP uptake (dark), endogenous peroxidase activity (white) and drug (grey) – TTX (1), lidocaine (2) or phenytoin (3). Each histobar represents the average±s.d. of data from at least six experiments. (D) Modified from Onganer and Djamgoz (2005).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2361510&req=5

fig1: Whole-cell patch-clamp recordings from SCLC H146 cells showing expression voltage activated inward (Na+) currents. (A) A family of membrane currents activated at different membrane potentials (values in mV indicated on the right). (B) Current–voltage relationship of voltage-gated Na+ currents. Circles – normal data; triangles – effect of 100 nM TTX; squares – effect of Na+-free medium (choline+ used as substitute). (C) Dose–response curve for TTX-induced suppression of the Na+ current, I (%) expressed as a percentage of the control value. (A–C) Modified from Blandino et al (1995). (D) Effects of 100 nM TTX (1), 200 nM lidocaine (2) and 200 nM phenytoin (3) on endocytic membrane activity (HRP uptake) into the SCLC cell line, H510 (left-hand sets of histobars) and the normal airway epithelial cell line, 16HBE14o (right-hand sets of histobars). OD540, optical density of HRP content of cell lysates. Each data set of three histobars shows the effects of the following: HRP uptake (dark), endogenous peroxidase activity (white) and drug (grey) – TTX (1), lidocaine (2) or phenytoin (3). Each histobar represents the average±s.d. of data from at least six experiments. (D) Modified from Onganer and Djamgoz (2005).

Mentions: Voltage-activated ion channels are a hallmark of neuronal excitability. In particular, VGSCs are necessary for initiation and conduction of regenerative potentials and VGCCs are frequently involved in secretion. Ion channel activity can be controlled by mitogens and oncogenes, and itself can affect metastatic cell behaviour, including proliferation. A high level VGSC and VGCC expression and electrophysiological activity, similar to those in excitable tissues, have been associated with human SCLC cells (Pancrazio et al, 1989; Blandino et al, 1995) (Figure 1A and B). These VGSCs appeared to be a mixture of tetrodotoxin (TTX)-sensitive and TTX-resistant channels, with a net IC50 of ∼100 nM (Blandino et al, 1995; Figure 1B and C). However, the functional role that these channels could play in SCLC behaviour is unknown. Interestingly, similar upregulation of VGSC expression/activity has been found in human metastatic prostate cancer in vitro (Laniado et al, 1997) and in vivo (Diss et al, 2005). Moreover, blockage of VGSC activity by the highly specific TTX suppressed a variety of cellular behaviours that would be involved in the metastatic cascade, including process extension, directional motility (e.g. Djamgoz et al, 2001), secretory membrane activity (e.g. Krasowska et al, 2004), adhesion (Mycielska et al, 2004), gene expression (e.g. Mycielska et al, 2005) and invasiveness in vitro (e.g. Laniado et al, 1997). Emerging data suggest that there is a comparable situation in metastatic human breast cancer cells (Fraser et al, 2005).


Neuronal characteristics of small-cell lung cancer.

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

Whole-cell patch-clamp recordings from SCLC H146 cells showing expression voltage activated inward (Na+) currents. (A) A family of membrane currents activated at different membrane potentials (values in mV indicated on the right). (B) Current–voltage relationship of voltage-gated Na+ currents. Circles – normal data; triangles – effect of 100 nM TTX; squares – effect of Na+-free medium (choline+ used as substitute). (C) Dose–response curve for TTX-induced suppression of the Na+ current, I (%) expressed as a percentage of the control value. (A–C) Modified from Blandino et al (1995). (D) Effects of 100 nM TTX (1), 200 nM lidocaine (2) and 200 nM phenytoin (3) on endocytic membrane activity (HRP uptake) into the SCLC cell line, H510 (left-hand sets of histobars) and the normal airway epithelial cell line, 16HBE14o (right-hand sets of histobars). OD540, optical density of HRP content of cell lysates. Each data set of three histobars shows the effects of the following: HRP uptake (dark), endogenous peroxidase activity (white) and drug (grey) – TTX (1), lidocaine (2) or phenytoin (3). Each histobar represents the average±s.d. of data from at least six experiments. (D) Modified from Onganer and Djamgoz (2005).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Whole-cell patch-clamp recordings from SCLC H146 cells showing expression voltage activated inward (Na+) currents. (A) A family of membrane currents activated at different membrane potentials (values in mV indicated on the right). (B) Current–voltage relationship of voltage-gated Na+ currents. Circles – normal data; triangles – effect of 100 nM TTX; squares – effect of Na+-free medium (choline+ used as substitute). (C) Dose–response curve for TTX-induced suppression of the Na+ current, I (%) expressed as a percentage of the control value. (A–C) Modified from Blandino et al (1995). (D) Effects of 100 nM TTX (1), 200 nM lidocaine (2) and 200 nM phenytoin (3) on endocytic membrane activity (HRP uptake) into the SCLC cell line, H510 (left-hand sets of histobars) and the normal airway epithelial cell line, 16HBE14o (right-hand sets of histobars). OD540, optical density of HRP content of cell lysates. Each data set of three histobars shows the effects of the following: HRP uptake (dark), endogenous peroxidase activity (white) and drug (grey) – TTX (1), lidocaine (2) or phenytoin (3). Each histobar represents the average±s.d. of data from at least six experiments. (D) Modified from Onganer and Djamgoz (2005).
Mentions: Voltage-activated ion channels are a hallmark of neuronal excitability. In particular, VGSCs are necessary for initiation and conduction of regenerative potentials and VGCCs are frequently involved in secretion. Ion channel activity can be controlled by mitogens and oncogenes, and itself can affect metastatic cell behaviour, including proliferation. A high level VGSC and VGCC expression and electrophysiological activity, similar to those in excitable tissues, have been associated with human SCLC cells (Pancrazio et al, 1989; Blandino et al, 1995) (Figure 1A and B). These VGSCs appeared to be a mixture of tetrodotoxin (TTX)-sensitive and TTX-resistant channels, with a net IC50 of ∼100 nM (Blandino et al, 1995; Figure 1B and C). However, the functional role that these channels could play in SCLC behaviour is unknown. Interestingly, similar upregulation of VGSC expression/activity has been found in human metastatic prostate cancer in vitro (Laniado et al, 1997) and in vivo (Diss et al, 2005). Moreover, blockage of VGSC activity by the highly specific TTX suppressed a variety of cellular behaviours that would be involved in the metastatic cascade, including process extension, directional motility (e.g. Djamgoz et al, 2001), secretory membrane activity (e.g. Krasowska et al, 2004), adhesion (Mycielska et al, 2004), gene expression (e.g. Mycielska et al, 2005) and invasiveness in vitro (e.g. Laniado et al, 1997). Emerging data suggest that there is a comparable situation in metastatic human breast cancer cells (Fraser et al, 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.

Show MeSH
Related in: MedlinePlus