De novo synthesis of C4.4A in hepatocellular carcinoma promotes migration and invasion of tumor cells

Görtz,Magdalena; Galli,Uwe; Longerich,Thomas; Zöller,Margot; Erb,Ulrike; Schemmer,Peter

doi:10.3892/or.2017.5980

De novo synthesis of C4.4A in hepatocellular carcinoma promotes migration and invasion of tumor cells

Authors:
- Magdalena Görtz
- Uwe Galli
- Thomas Longerich
- Margot Zöller
- Ulrike Erb
- Peter Schemmer
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Affiliations: Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany, Tumor Cell Biology, Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
Published online on: September 20, 2017 https://doi.org/10.3892/or.2017.5980
Pages: 2697-2704
Copyright: © Görtz et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

C4.4A is a glycoprotein that is upregulated in several human malignancies, including colorectal, breast and renal cell carcinomas. Due to its highly restricted expression in healthy tissue, C4.4A was proposed as a potential diagnostic marker. Thus, the present study was designed to evaluate C4.4A expression and function in hepatocellular carcinoma (HCC) for the first time. Immunohistochemistry was performed to detect expression of C4.4A in human sections of healthy liver, primary HCC in the liver and metastatic HCC in the lung. To assess the contribution of C4.4A to HCC progression proliferation, apoptosis, migration and invasion assays were performed with C4.4A knockdown Huh7 and HepG2 cells. C4.4A is absent in healthy liver tissue. However, intense expression was seen in 59% of primary HCCs and strong expression in 80% of HCC lung metastases. C4.4A expression was also observed in human HCC cell lines, which strongly increased under hypoxic conditions. A C4.4A knock-down revealed that C4.4A is involved in both migration and invasion of HCC cells. Taken together, C4.4A expression in both primary and metastatic HCC suggests its potential value as a diagnostic marker for HCC. Due to its absence in healthy liver tissue, C4.4A might even serve as a possible therapeutic target, particularly for metastatic HCC.

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