Dayoub, Rania and Wagner, Hannah and Bataille, Frauke and Stoeltzing, Oliver and Spruss, Thilo and Buechler, Christa and Schlitt, Hans-Juergen and Weiss, Thomas S. (2011) Liver Regeneration Associated Protein (ALR) Exhibits Antimetastatic Potential in Hepatocellular Carcinoma. MOLECULAR MEDICINE, 17 (3-4). pp. 221-228. ISSN 1076-1551, 1528-3658
Full text not available from this repository. (Request a copy)Abstract
Augmenter of liver regeneration (ALR), which is critically important in liver regeneration and hepatocyte proliferation, is highly expressed in cirrhotic livers and hepatocellular carcinomas (HOC). In the current study, the functional role of ALR in hepatocancerogenesis was analyzed in more detail. HepG2 cells, in which the cytosolic 15 kDa ALR isoform was reexpressed stably, (HepG2-ALR) were used in migration and invasion assays using modified Boyden chambers. Epithelial-mesenchymal transition (EMT) markers were determined in HepG2-ALR cells in vitro and in HepG2-ALR tumors grown in nude mice. ALR protein was quantified in HOC and nontumorous tissues by immunohistochemistry. HepG2-ALR, compared with HepG2 cells, demonstrated reduced cell motility and increased expression of the epithelial cell markers E-cadherin and Zona occludens-1 (ZO-1), whereas SNAIL a negative regulator of E-cadherin, was diminished. Matrix metalloproteinase MMP1 and MMP3 mRNA expression and activity were reduced. HepG2-ALR cell-derived subcutaneously grown tumors displayed fewer necrotic areas, more epithelial-like cell growth and fewer polymorphisms and atypical mitotic figures than tumors derived from HepG2 cells. Analysis of tumor tissues of 53 patients with HOC demonstrated an inverse correlation of ALR protein with histological angioinvasion and grading. The 15 kDa ALR isoform was found mainly in HCC tissues without histological angioinvasion 0. In summary the present data indicate that cytosolic ALR reduces hepatoma cell migration, augments epithelial growth and, therefore, may act as an antimetastatic and EMT reversing protein. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molrned.2010.00117
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL-MESENCHYMAL TRANSITION; MIGRATION INHIBITORY FACTOR; DISULFIDE BOND FORMATION; SULFHYDRYL OXIDASE; TUMOR PROGRESSION; HUMAN HEPATOCYTES; HEPATOMA-CELL; HEPATOTROPHIC FACTOR; INTERMEMBRANE SPACE; AUGMENTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Kinder- und Jugendmedizin Medicine > Lehrstuhl für Pathologie Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jun 2020 10:20 |
| Last Modified: | 24 Jun 2020 10:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21181 |
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