HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells.
Human hepatocarcinoma-intestine-pancreas (HIP) cDNA, isolated from a hepatocellular carcinoma, encodes a C-type lectin. According to published cDNA sequences, HIP protein is identical to human pancreatitis-associated protein (PAP). In these sequences, a putative signal peptide and the carbohydrate recognition domain (CRD) can be recognized. In the present study, we established transgenic mice to drive the production of soluble recombinant HIP/PAP protein in the milk of lactating animals; using this model, we showed that HIP/PAP protein was secreted after suitable cleavage of the potential signal peptide. Moreover, we also produced HIP/PAP protein by Escherichia coli cultures performed to generate specific antibodies. These antibodies enabled the detection of HIP/PAP protein in normal intestine and pancreas (both in endocrine and exocrine cells), e.g., intestinal neuroendocrine and Paneth cells, pancreatic islets of Langerhans, and acinar cells. HIP/PAP protein was also identified in the cytoplasm of tumoral hepatocytes but not in nontumoral hepatocytes. Finally, HIP/PAP protein activity was tested and we showed that HIP/PAP induced the adhesion of rat hepatocytes and bound strongly to extracellular matrix proteins (laminin-1, fibronectin), less strongly to type I and IV collagen, and not at all to heparan sulfate proteoglycan. In conclusion, these results showed that HIP/PAP protein was matured on secretion. We also demonstrated that HIP/PAP protein was specifically expressed in hepatocarcinoma cells and interacted with rat hepatocytes and the extracellular matrix. Taken overall, these results suggest that HIP/PAP protein may be of potential importance to liver cell differentiation/proliferation.
Christa
L
L
Institut National de la Santé et de la Recherche Médicale Unité 370, Centre Hospitalier Universitaire Necker, Paris, France.
Carnot
F
F
Simon
M T
MT
Levavasseur
F
F
Stinnakre
M G
MG
Lasserre
C
C
Thepot
D
D
Clement
B
B
Devinoy
E
E
Brechot
C
C
D000209:Acute-Phase Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; D011994:Recombinant Proteins; C490253:Reg3b protein, mouse; C000612144:Reg3b protein, rat