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ID 116612
Author
Tokuda, Kazunori Tokushima University
Miyazaki, Katsuki Tokushima University
Keywords
hepatocellular carcinoma
osteopontin
cancer associated fibroblast
tumor associated macrophage
tumor microenvironment
Content Type
Journal Article
Description
Background: Cancer-tumor associated macrophage (TAM)-cancer associated fibroblast (CAF) interactions are an important factor in the tumor microenvironment of hepatocellular carcinoma.
Materials and Methods: Hepatic stellate cells (HSCs) were cultured with cancer cell-conditioned medium (Ca.-CM), TAM-CM and CAF-CM, and the expression of CAF markers were evaluated by RT-PCR. Whether HSCs cultured with Ca.-CM, TAM-CM and CAF-CM contributed to the enhanced malignancy of cancer cells was examined using proliferation, invasion and migration assays. Furthermore, the differences between these three types of CM were evaluated using cytokine arrays.
Results: HSCs cultured with Ca.-CM, TAM-CM and CAF-CM showed significantly increased mRNA expression of αSMA, FAP and IL-6. All HSCs cultured with each CM exhibited significantly increased proliferation, invasion and migration of cancer cells. The osteopontin concentration was significantly higher in HSCs cultured with TAM-CM than the other CAF-CMs. Osteopontin inhibition significantly reduced osteopontin secretion from HSCs cultured with TAM-CM and suppressed the proliferation and invasion of cancer cells enhanced by HSCs cultured with TAM-CM.
Conclusions: We observed enhanced osteopontin secretion from TAMs, and this increased osteopontin further promoted osteopontin secretion from HSCs cultured with TAM-CM, leading to increased malignancy. For the first time, we demonstrated the importance of cancer-TAM-CAF interactions via osteopontin in hepatocellular carcinoma.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
12
Issue
4
Start Page
333
End Page
343
Published Date
2021-02-16
Rights
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
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departments
Medical Sciences
University Hospital