Neurotrophin system activation in pleural effusions.
Neurotrophins (NTs) expression was assessed in malignant and non-malignant pleural effusions (inflammatory exudates and transudates). Enzyme-linked immunosorbent assay, in malignant exudates from small and non-small cell lung cancer (SCLC and NSCLC), detected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their levels are higher as compared with inflammatory and transudative effusions. By immunoblots, in cultured cancer cells coming from malignant pleural effusions, NTs and low- and high-affinity NT receptors were detected in a percentage of SCLC and NSCLC. Proliferation assay demonstrated that BDNF significantly increased cancer cell proliferation in vitro, on the contrary, NT-3 reduced cancer cell growth rate and NGF did not modify cell growth. Moreover, NGF protects cells from death during starvation. These effects are reverted by the addition of NT receptor antagonists. Cultured cancer cells injected into the lung of immunodeficient mice generate lung tumors expressing NTs and NT receptors. These findings suggest that NTs may be able to modulate cancer cell behavior and their growth.
Ricci
Alberto
A
Università La Sapienza, Rome, Italy. alberto.ricci@uniroma1.it
Mariotta
Salvatore
S
Pompili
Elena
E
Mancini
Rita
R
Bronzetti
Elena
E
De Vitis
Claudia
C
Pisani
Lara
L
Cherubini
Emanuela
E
Bruno
Pierdonato
P
Gencarelli
Giorgetta
G
Giovagnoli
Maria R
MR
Terzano
Claudio
C
Ciliberto
Gennaro
G
Giarnieri
Enrico
E
Fumagalli
Lorenzo
L
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D010996:Pleural Effusion / Q000235:genetics / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB