Hip/pap is an adhesive molecule expressed in hepatocellular
carcinoma, normal paneth and pancreatic cells..
Christa, Laurence, Fran[cedilla]coise Carnot, Marie
-Th[acute]er[grave]ese Simon, Fran[cedilla]coise Levavasseur, Marie
-Georges Stinnakre, Chantal Lasserre, Dominique Thepot, Bruno Clement,
Eve Devinoy, Christian Brechot.
Institut National de la Sant[acute]e Et de la Recherche
M[acute]edicale U-370 and Liver Unit, CHU Necker, 156 rue de
Vaugirard, 75742 Paris cedex 15, France, Tel.: 40 61 56 45. Fax: 40
61 55 81, H[circumflex]opital Laennec, F-75007 Paris Cedex 15,
France, Unit[acute]e de recherches h[acute]epatologiques, Institut
National de la Sant[acute]e Et de la Recherche M[acute]edicale U-49,
H[circumflex]opital Pontchaillou, 35033 Rennes, France, Unit[acute]e
de diff[acute]erenciation cellulaire, Institut National de Recherche
Agronomique, 78350 Jouy-en-Josas, France
APStracts 3:0124G, 1996.
Human HIP cDNA, isolated from an 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 E. 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. intestine neuroendocrine and Paneth cells, pancreatic
Langerhans islets and acinar cells. HIP/PAP protein was also
identified in the cytoplasm of tumoral hepatocytes, but not in non
-tumoral 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 upon secretion. We also
demonstarated 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.
Received 25 October 1995; accepted in final form 21 May 1996.
APS Manuscript Number G466-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96