Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

Abstract

Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.

Mutations in TJP2 cause progressive cholestatic liver disease

“…1d). As expected, CLDN2 showed a pericanalicular staining pattern in controls 8 . This distribution was preserved in patient material with an apparent increase in abundance (Figure 1c).…”

“…They have been demonstrated to bind to the PDZ1 domain of TJPs in vitro 7 . Claudin-1 (CLDN1) and claudin-2 (CLDN2) are known to be expressed in the liver 6 and to manifest different sub-cellular localisations 8 . Immunohistochemical analysis of CLDN1 expression showed tight-junction marking in controls.…”

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

“…The claudin-1 protein is involved in maintaining cellular adhesion and the formation of cell junctions (Gunzel and Yu, 2013, Morita et al, 1999), and loss of claudin-1 in the liver can promote metastasis (Georges et al, 2012, Holczbauer et al, 2013). PFOA and PFOS also caused an induction of the AKR1B10 gene (Figure 6B) that is associated with the progression of hepatocellular carcinoma (Matkowskyj et al, 2014).…”

Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact

“…In fact, specific claudin family members especially claudin-3 and -4 have rather been documented to be upregulated in multiple cancer types including prostate, pancreatic and ovarian cancer Q5 (Fig. 1) [22][23][24]. Importantly, sole reliance upon the total cellular levels of claudin expression in cancer cells may elude us from true understanding of the role claudin proteins in cancer regulation, as sheer deregulation of these proteins from their membrane localization (without a decrease in transcription and/or protein synthesis) can modulate the cellular homeostasis in a significant manner.…”