Modeling of hepatocytes proliferation isolated from proximal and distal zones from human hepatocellular carcinoma lesion

Mauro Montalbano, Giuseppe Curcurù, Ali Shirafkan, Renza Vento, Cristiana Rastellini, Luca Cicalese

Research output: Contribution to journalArticle

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Abstract

Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liver in relation to their distance from the HCC lesion. In this study, hepatocytes from 10 patients with cirrhosis and HCC undergoing surgical resections from specimens obtained at a proximal (CP) and distal (CD) distance from the HCC lesion were isolated and placed in primary culture. CP hepatocytes (CP-Hep) were isolated between 1 to 3 cm (leaving at least 1cm margin to avoid cancer cells and/or satellite lesions), while CD hepatocytes (CD-Hep) were isolated from more than 5 cm or from the contralateral-lobe. A statistical model was built to analyze the proliferation rates of these cells and we evaluated expression of HCC markers (Glypican- 3 (GPC3), áSmooth Muscle Actin (á-SMA) and PCNA). We observed a significant difference in proliferation and in-vitro growth showing that CP-Hep had a proliferation pattern and rate significantly different than CD-Hep. Based on these data, this model can provide information to predict growth of human hepatocytes in primary culture in relation to their precancerous state with significant differences in the HCC markers expression. This model provides an important innovative tool for in-vitro analysis of HCC.

Original languageEnglish (US)
Article numbere0153613
JournalPLoS One
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2016

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hepatoma
lesions (animal)
hepatocytes
Hepatocytes
Hepatocellular Carcinoma
Liver
Growth
Glypicans
liver
human growth
Proliferating Cell Nuclear Antigen
Statistical Models
resection
cells
Research laboratories
statistical models
smooth muscle
actin
Smooth Muscle
Muscle

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Modeling of hepatocytes proliferation isolated from proximal and distal zones from human hepatocellular carcinoma lesion. / Montalbano, Mauro; Curcurù, Giuseppe; Shirafkan, Ali; Vento, Renza; Rastellini, Cristiana; Cicalese, Luca.

In: PLoS One, Vol. 11, No. 4, e0153613, 01.04.2016.

Research output: Contribution to journalArticle

Montalbano, Mauro ; Curcurù, Giuseppe ; Shirafkan, Ali ; Vento, Renza ; Rastellini, Cristiana ; Cicalese, Luca. / Modeling of hepatocytes proliferation isolated from proximal and distal zones from human hepatocellular carcinoma lesion. In: PLoS One. 2016 ; Vol. 11, No. 4.
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abstract = "Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liver in relation to their distance from the HCC lesion. In this study, hepatocytes from 10 patients with cirrhosis and HCC undergoing surgical resections from specimens obtained at a proximal (CP) and distal (CD) distance from the HCC lesion were isolated and placed in primary culture. CP hepatocytes (CP-Hep) were isolated between 1 to 3 cm (leaving at least 1cm margin to avoid cancer cells and/or satellite lesions), while CD hepatocytes (CD-Hep) were isolated from more than 5 cm or from the contralateral-lobe. A statistical model was built to analyze the proliferation rates of these cells and we evaluated expression of HCC markers (Glypican- 3 (GPC3), {\'a}Smooth Muscle Actin ({\'a}-SMA) and PCNA). We observed a significant difference in proliferation and in-vitro growth showing that CP-Hep had a proliferation pattern and rate significantly different than CD-Hep. Based on these data, this model can provide information to predict growth of human hepatocytes in primary culture in relation to their precancerous state with significant differences in the HCC markers expression. This model provides an important innovative tool for in-vitro analysis of HCC.",
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