TRANSFORMATION OF PRIMARY HUMAN HEPATOCYTES IN HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Currently, there is limited knowledge of neoplastic transformation of hepatocytes in HCC. In clinical practice, the high rate of HCC local recurrence suggests the presence of different hepatocyte populations within the liver and particularly in the tumor proximity. This study aims to investigate primary human hepatocytes culture obtained from liver specimens of patients affected by cirrhosis and HCC, their proliferation and transformation. Liver samples were obtained from seven HCC cirrhotic patients and from three patients with normal liver (NL). Immediately after surgery, cell outgrowth and primary cultures were obtained from the HCC lesion, the cirrhotic tissue proximal (CP: 1 to 3 cm) and distal (CD: >5 cm) to the margin of the neoplastic lesion, or from NL. Cells were kept in culture for 16 weeks. Morphologic analyses were performed and proliferation rate of the different cell populations compared over time. Glypican-3, Heppar-1, Arginase-1 and CD-44 positivity were tested. The degree of invasiveness of cells acquiring neoplastic characteristics was studied with a trans-well migration assay. We observed that HCC cells maintained their morphology and unmodified neoplastic characteristics when cultured. Cells isolated from CP, showed a progressive morphologic transformation in HCC-like cells accompanied by modification of markers expression with signs of invasiveness. Absence of HCC contamination in the CP isolates was confirmed. In CD samples some of these characteristics were present and at significantly lower levels. With this study, we are the first to have identified and described the existence of human hepatocytes near the cancerous lesion that can transform in HCC in- vitro.

Name thesis:degree_name

Neuroscience (Doctoral)

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Montalbano, Mauro

Advisor dc:contributor.advisor

• Cicalese, Luca

Committee members dc:contributor.committeemember

• Rastellini, Cristiana
• Cornelis, Elferink
• Beretta, Laura
• Taglialatela, Giulio

• Glypican-3 Hepatocellular carcinoma Cancer

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/11281

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/11281