Peptide products of the neurotrophin-inducible gene vgf are produced in human neuroendocrine cells from early development and increase in hyperplasia and neoplasia.
BACKGROUND
Although the neurotrophin-inducible gene vgf is expressed in mammalian neurons and endocrine cells, limited data is available in man.


OBJECTIVE
The objective of the study was to map proVGF peptides in human endocrine cells during development, adulthood, hyperplasia, and tumors.


METHODS
Antisera were generated against peptides related to internal cleavage or cleavage-amidation sites (rat proVGF(422-430) and human proVGF(298-306)-NH2) and the proVGF C-terminal ending (human proVGF(607-615)). Developing and normal adult endocrine cells, hyperplastic endocrine lesions (thyroid, parathyroid, lung, and stomach), and 120 tumors (102 endocrine) were studied. Immunogold electron microscopy was performed on normal adult pancreas and gut, and Western blotting was performed on extracts of control tissues and endocrine tumors.


RESULTS
proVGF fragments were revealed in developing pituitary, gut, pancreas, and adrenal medulla from 10 gestational weeks, in normal adult pituitary and adrenal medulla, pancreatic glucagon, and insulin cells and gut serotonin cells, in hyperplastic thyroid calcitonin cells, lung P cells, gastric enterochromaffin-like cells, and gastrin cells, and in 88 of 102 endocrine tumors. At electron microscopy proVGF immunoreactivity was restricted to electron-dense granules. Western blotting revealed large molecular weight forms and cleavage fragments in both control tissues and tumor extracts.


CONCLUSIONS
proVGF-related peptides are present in endocrine cells early during development and adulthood and increase in hyperplasia and tumors, and proVGF fragments could be novel diagnostic tools for endocrine cells and related lesions, including tumors.
Rindi
Guido
G
Department of Pathology and Laboratory Medicine, University of Parma, 43100 Parma, Italy. guido.rindi@unipr.it
Licini
Lisa
L
Necchi
Vittorio
V
Bottarelli
Lorena
L
Campanini
Nicoletta
N
Azzoni
Cinzia
C
Favret
Maurizio
M
Giordano
Giovanna
G
D'Amato
Filomena
F
Brancia
Carla
C
Solcia
Enrico
E
Ferri
Gian-Luca
GL
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D004701:Endocrine Gland Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004703:Endocrine System / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D009414:Nerve Growth Factors / Q000378:metabolism*; D010235:Paraganglioma / Q000378:metabolism / Q000473:pathology; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology
D009414:Nerve Growth Factors; C510637:VGF protein, human