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Cellular Oncology
Published in: Cellular Oncology 1/2016

01-02-2016 | Original Paper

HepG2 cells acquire stem cell-like characteristics after immune cell stimulation

Authors: Hang Wang, Miqing Yang, Ling Lin, Hongzhen Ren, Chaotong Lin, Suling Lin, Guoying Shen, Binfeng Ji, Chun Meng

Published in: Cellular Oncology | Issue 1/2016

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Abstract

Background

The presence of cancer stem cells (CSCs) is currently regarded as one of the main culprits of tumor formation and therapy failure. It is known that chronic inflammation is associated with CSCs, but it is not clear yet how inflammation affects the development of CSCs. In the present study we aimed to examine the relationship between cancer cell stimulation mediated by immune cells and the acquisition of a CSC-like phenotype.

Methods

Cancer cells derived from single hepatocarcinoma HepG2 cells were treated with mouse splenic B cells (MSBCs) and mouse peritoneal macrophage cells (MPMCs), respectively. The stem cell-like characteristics of the resulting HepG2 cells (MSBC-HepG2 and MPMC-HepG2) were evaluated using different assays, including biomarker assays, in vitro tumoroid and colony forming assays, in vivo tumor forming assays and signal transduction pathway activation assays.

Results

Various stemness characteristics of HepG2 cells, including self-renewal, proliferation, chemoresistance and tumorigenicity were evaluated. The expression levels of stemness-related genes and its encoded proteins in the MSBC-HepG2 and MPMC-HepG2 cells were assessed using RT-PCR and FACS analyses. We found that MSBC-HepG2 and MPMC-HepG2 cells possess hepatic CSC properties, including persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and over-expression of CSC-related genes and proteins (i.e., EpCAM, ALDH, CD133 and CD44), compared to the parental cells. We also found that 1x103 MSBC-HepG2 and MPMC-HepG2 cells were able to form tumors in NOD/SCID mice and that the Notch and SHH signaling pathways were highly activated in MSBC-HepG2 cells.

Conclusions

We conclude that the immune system may have a double-edge effect on cancer development. On one hand, immune cells such as B lymphocytes and macrophages may recognize, attack and eliminate cancer cells, whereas on the other hand, they may promote a subset of cancer cells to acquire stem cell-like characteristics.
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Metadata
Title
HepG2 cells acquire stem cell-like characteristics after immune cell stimulation
Authors
Hang Wang
Miqing Yang
Ling Lin
Hongzhen Ren
Chaotong Lin
Suling Lin
Guoying Shen
Binfeng Ji
Chun Meng
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2016
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0249-1

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