HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells
HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells
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DOI：
10.1152/ajpgi.1996.271.6.g993
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发表时间：
1996-12-01
影响因子：
4.5
通讯作者：
Brechot, C
中科院分区：
文献类型：
--
作者：
Christa, L;Carnot, F;Brechot, C
人肝癌-肠-胰腺(HIP)基因是从肝细胞癌中分离出来的，编码一个C型凝集素。根据已发表的cDNA序列，HIP蛋白与人胰腺炎相关蛋白(PAP)完全相同。在这些序列中，可以识别一个假定的信号肽和碳水化合物识别结构域(CRD)。在本研究中，我们建立了转基因小鼠来驱动哺乳动物乳汁中可溶性重组HIP/PAP蛋白的产生，利用这个模型，我们证明了HIP/PAP蛋白是在适当切割潜在信号肽后分泌出来的。此外，我们还通过大肠杆菌培养产生了HIP/PAP蛋白，以产生特异性抗体。这些抗体能够在正常肠道和胰腺(包括内分泌和外分泌细胞)中检测到HIP/PAP蛋白，例如肠神经内分泌和潘氏细胞、朗格汉斯胰岛和腺泡细胞。HIP/PAP蛋白在肿瘤肝细胞胞浆中也有表达，而在非肿瘤肝细胞中未见表达。HIP/PAP蛋白活性测定表明，HIP/PAP可诱导大鼠肝细胞黏附，与细胞外基质蛋白(层粘连蛋白-L、纤维连接蛋白)结合较强，与I型和IV型胶原结合较弱，与硫酸乙酰肝素蛋白多糖无明显结合。这些结果表明，HIP/PAP蛋白在分泌时成熟。我们还证实了HIP/PAP蛋白在肝癌细胞中特异表达，并与大鼠肝细胞和细胞外基质相互作用。综上所述，这些结果提示HIP/PAP蛋白可能对肝细胞的分化/增殖具有潜在的重要作用。
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-l, 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.