Detection of the neural cell adhesion molecule (NCAM) in serum of patients with small-cell lung cancer (SCLC) with “limited” or “extensive” disease, and bone-marrow infiltration

Ledermann, JA; Pasini, Felice; Olabiran, Y.; Pelosi, Giuseppe

doi:10.1002/ijc.2910570710

Cited by 29 publications

(14 citation statements)

References 16 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With regard to current biomarkers used in the clinic, this is the expected concentration range, giving us hope that new lung cancer markers should be detectable in serum. Through our method, we successfully identified proteins that are putative or currently used as biomarkers of lung cancer, including CEA (27,28), pro-GRP (29,31), SCC antigen (47,48), tumor M2-PK (49), NCAM (35)(36)(37), chromogranin A (29), and chromogranin B (30). In addition, we identified putative markers previously reported in lung-related proteomics studies such as member C1 of aldo-keto reductase family 1 identified by Huang et al (25) as dihydrodiol dehydrogenase and matrix metallopeptidase 1 found to be overexpressed in lung cancer patients and especially in late stage (18).…”

Section: Discussionmentioning

confidence: 99%

Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines

Planque

Kulasingam

Smith

et al. 2009

Molecular & Cellular Proteomics

133

107

View full text Add to dashboard Cite

Detection of lung cancer at an early stage is necessary for successful therapy and improved survival rates. We performed a bottom-up proteomics analysis using a twodimensional LC-MS/MS strategy on the conditioned media of four lung cancer cell lines of different histological backgrounds (non-small cell lung cancer: H23 (adenocarcinoma), H520 (squamous cell carcinoma), and H460 (large cell carcinoma); small cell lung cancer: H1688) to identify secreted or membrane-bound proteins that could be useful as novel lung cancer biomarkers. Proteomics analysis of the four conditioned media allowed identification of 1,830 different proteins (965, 871, 726, and 847 from H1688, H23, H460, and H520, respectively). All proteins were assigned a subcellular localization, and 38% were classified as extracellular or membrane-bound. We successfully identified the internal control proteins (also detected by ELISA), kallikrein-related peptidases 14 and 11, and IGFBP2. We also identified known or putative lung cancer tumor markers such as squamous cell carcinoma antigen, carcinoembryonic antigen, chromogranin A, creatine kinase BB, progastrin-releasing peptide, neural cell adhesion molecule, and tumor M2-PK. To select the most promising candidates for validation, we performed tissue specificity assays, functional classifications, literature searches for association to cancer, and a comparison of our proteome with the proteome of lung-related diseases and serum. Five novel lung cancer candidates, ADAM-17, osteoprotegerin, pentraxin 3, follistatin, and tumor necrosis factor receptor superfamily member 1A were preliminarily validated in the serum of patients with lung cancer and healthy controls. Our results demonstrate the utility of this cell culture proteomics approach to identify secreted and shed proteins that are potentially useful as serologi-

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines

Planque

Kulasingam

Smith

et al. 2009

Molecular & Cellular Proteomics

133

107

View full text Add to dashboard Cite

show abstract

“…Ectodomain shedding of cell adhesion proteins such as carcinoembryonic antigen (CEA) (33,34), NCAM (35,36), or CD44 (37, 38) is linked to strong overexpression of these proteins in certain types of epithelial cancers, and the soluble forms of these proteins may serve as clinical tumor markers. We found previously that the cell adhesion molecule L1 is overexpressed in some renal tumors (2).…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte Growth Factor-induced Ectodomain Shedding of Cell Adhesion Molecule L1

Heiz

Grünberg

Schubiger

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The L1 cell adhesion molecule and its soluble form are tumor-associated proteins and potential markers for tumor staging as well as targets for therapeutic intervention. Soluble L1 is produced by metalloprotease-mediated ectodomain shedding of L1. We investigated effects of hepatocyte growth factor (HGF), a growth factor shown to increase invasiveness of renal carcinoma cells, on ectodomain shedding of L1 from these cells. All of the tested L1-positive renal carcinoma cell lines released a 180-kDa form of L1 into the medium. In the presence of serum, addition of HGF led to a dose-dependent increase in L1 shedding with a maximum reached at 5 ng/ml. In contrast, L1 shedding was inhibited by glial cell linederived neurotrophic factor (GDNF). The tyrosine kinase inhibitor Genistein reduced basal and HGFstimulated L1 shedding, indicating that protein phosphorylation is involved. To investigate the role of the L1 intracellular domain, two mutants of the L1 cytoplasmic part were constructed. L1trun lacking the complete intracellular domain showed enhanced basal shedding. In a L1YH mutant, containing the mutation tyrosine 1229 to histidine that deletes the ankyrin binding motif of L1, basal shedding was reduced. Disruption of actin assembly by cytochalasin D also reduced shedding of L1. These results indicate that the cytoplasmic domain regulates basal shedding of L1, and association with the cytoskeleton through the L1 ankyrin binding site is involved. HGF stimulated L1 shedding in both mutants, indicating that receptor-mediated phosphorylation in the L1 cytoplasmic domain is not required for HGF-stimulated shedding.The L1 cell adhesion molecule (L1) 1 was originally described as a protein of the nervous system, and mutated forms of L1 are linked to severe neurological pathologies referred to as MASA syndrome (1). A non-neuronal isoform of L1 lacking exons 2 and 27 is expressed at low levels in the normal adult human kidney (2) as well as during renal development (3). In contrast, high expression of L1 was found in 8 of 12 renal tumor cell lines and in some renal tumors (2). 2 It was shown that the cell-bound form of L1 can serve as a target for radioimmunodiagnosis of metastatic neuroblastoma (4), and L1 may also be a marker and therapeutic target for certain renal cancers.In cultured cell lines originating from a number of different tumors the L1 ectodomain was found to be cleaved proximal to the cell membrane by metalloproteases, followed by release of soluble L1 into the medium (5-7). Ectodomain shedding of L1 could be stimulated by phorbol esters and vanadate, indicating that phosphorylation events regulate L1 release (6). In cell culture soluble L1 substrate was found to stimulate cellular motility and migration (8). Release of soluble L1 is not restricted to cells in culture as soluble L1 was recently detected in serum samples of patients with ovarian and uterine tumors and is believed to lead to increased cell migration and metastatic spread in these malignancies (9).Here we investigated whether hepatocyte grow...

show abstract

“…it has been shown that the serum levels of polysialylated NCAM are elevated in adult patients with small-cell lung cancer (Jaques et al 1993) and multiple myeloma (Kaiser et al 1994). high levels being associated with a poor prognosis (Ledermann et al 1994: Smith et al, 1996.…”

mentioning

confidence: 99%

Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma

Glüer

Schelp²,

Madry³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Neuroblastoma cells express the polysiatylated form of the neural cell adhesion molecule (NCAM), which normally becomes restricted to a few neural tissues after embryogenesis. In this study, we investigated serum levels of polysialylated NCAM in 14 children with different grades and stages of neuroblastoma using an immunoluminescence assay, and compared the results to 269 healthy control subjects. Simultaneousty, the polysialylated NCAM content of the tumours was determined by immunohistochemistry. Serum levels were dramatcalty elevated (more than sixfold) in children with advanced stages and fatal courses of disease, whereas children with differentiated tumour types and limited disease had low or normal levels. Serum concentrations correlated with the polysialylated NCAM content of the tumours, and they decreased during successful therapy. We therefore suggest polysialylated NCAM to be a useful marker monitoring childhood neuroblastoma.

show abstract

Detection of the neural cell adhesion molecule (NCAM) in serum of patients with small-cell lung cancer (SCLC) with “limited” or “extensive” disease, and bone-marrow infiltration

Cited by 29 publications

References 16 publications

Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines

Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines

Hepatocyte Growth Factor-induced Ectodomain Shedding of Cell Adhesion Molecule L1

Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma

Contact Info

Product

Resources

About