Tumor stroma with senescence-associated secretory phenotype insteatohepatitic hepatocellular carcinoma

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486543.do
DOI
10.1371/journal.pone.0171922
Title
Tumor stroma with senescence-associated secretory phenotype insteatohepatitic hepatocellular carcinoma
Description
This research was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MISP) (Grant number:NRF-2012M3A9B6055350, to PYN). We declare that the funders had no rolein study design, data collection and analysis, decision to publish, orpreparation of the manuscript.
abstract
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SHHCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of a-smooth muscle actin (a-SMA), p21(Waf1/Cifi), y-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all). The numbers of a-SMA-positive cancer-associated fibroblasts (CAFs) (P= 0.049) and a-SMA-positive CAFs co-expressing p21(Waf1/Cif1) (P = 0.038), y-H2AX (P = 0.065), and IL-6 (P = 0.048) were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of aSMA-positive stellate cells expressing y-H2AX and p21(Waf1/Cif1) than that from C-HCCs (P <0.05, all). In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.
provenance
Made available in Cube on 2018-09-28T16:10:26Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Jee San
Yoo, Jeong Eun
Kim, Haeryoung
Rhee, Hyungjin
Koh, Myoung Ju
Nahm, Ji Hae
Choi, Jin Sub
Lee, Kee-Ho
Park, Young Nyun
orcid
Rhee, Hyungjin/0000-0001-7759-4458
accessioned
2018-09-28T16:10:26Z
available
2018-09-28T16:10:26Z
issued
2017
citation
PLOS ONE(12): 3
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486543.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274063
Jurisdiction
Rep.of Korea
Project Name
Project of Yonsei Medical Science
rights
openAccess
type
article


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