Immunolocalization of a new intestinal antiproliferative factor in human intestinal epithelial cells.
A new intestinal antiproliferative factor (IAF) with an approximate molecular weight of 120 kDa has been purified from the human small intestine. This factor blocks the progression of human colon adenocarcinoma cells HT-29 from the G1 to the S phase. IAF, specific of the lower part of the digestive tract, was detected rather late in mouse embryonic development. For determination of the specific intestinal cell producing IAF, long-term differentiated mucus-secreting HT-29 Cl 16E and enterocytic HT-29 Cl 19A cell lines were used. IAF is synthesized exclusively in the intestinal goblet cells; it is processed in the RER and Golgi complex before being excreted in secretory vesicles independently of mucin secretion. IAF can be considered a growth inhibitor of intestinal proliferation for the same reason as TGF-beta. However, two features differentiate it from TGF-beta: (1) the intestinal cell type synthesizing it, and (2) the delay in its expression in embryonic development. Particular interest was paid to IAF expression in pathological conditions using human colon biopsies. IAF was consistently recovered in biopsies from patients with inflammatory bowel diseases and benign tumors, but it was never detected in malignant tumors. IAF could represent a marker of colon cancer owing to its absence from malignant tumors.
Lavagna
Christian
C
Laboratory of Gastroenterology and Nutrition, Faculty of Medicine, Nice, France.
Strup
Carine
C
Rampal
Agnes
A
Hofman
Paul
P
Bardon
Sylvie
S
Rampal
Patrick
P
Poirée
Jean-Claude
JC
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000502:physiology; D003108:Colonic Diseases / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D016193:G1 Phase / Q000502:physiology; D020397:Goblet Cells / Q000378:metabolism; D006131:Growth Inhibitors / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008970:Molecular Weight; D009077:Mucins / Q000378:metabolism
D006131:Growth Inhibitors; D008565:Membrane Proteins; D009077:Mucins; C031717:growth inhibitory proteins