Transition into inflammatory cancer-associated adipocytes in breastcancer microenvironment requires microRNA regulatory mechanism

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486457.do
DOI
10.1371/journal.pone.0174126
Title
Transition into inflammatory cancer-associated adipocytes in breastcancer microenvironment requires microRNA regulatory mechanism
Description
This work was supported by the Research Resettlement Fund for the NewFaculty of Seoul National University, Basic Science Research Programthrough the National Research Foundation of Korea (NRF) funded by theMinistry of Education, Science and Technology (2012R1A1A2005929,2015R1C1A1A02036629, and 2015R1D1A1A02061904), by the grant from theNational R&D Program for Cancer Control, Ministry for Health andWelfare, Republic of Korea (A1520250), and by the grant of the KoreaHealth Industry Development Institute (KHIDI), funded by the Ministry ofHealth & Welfare, Republic of Korea (HI13C2148).
abstract
The role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood. We reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro. The CAAs in human breast cancers showed heterogeneous topographic relationship with breast cancer cells within the breast microenvironment. The CAAs exhibited the characteristics of de-differentiation determined by their microscopic appearance and the expression levels of adipogenic markers. Additionally, the 3T3-L1 adipocytes indirectly co-cultured with breast cancer cells showed up-regulation of inflammation-related genes including Il6 and Ptx3. The up-regulation of IL6 in CAA was further observed in human breast cancer tissues. miRNA array of indirectly co-cultured 3T3-L1 cells showed increased expression of mmu-miR-5112 which may target Cpeb1. Cpeb1 is a negative regulator of Il6. The suppressive role of mmu-miR-5112 was confirmed by dual luciferase reporter assay, and mmu-miR-5112-treated adipocytes showed up-regulation of Il6. The transition of adipocytes into more inflammatory CAA resulted in proliferation-promoting effect in ER positive breast cancer cells such as MCF7 and ZR-75-1 but not in ER negative cells. In this study, we have determined the de-differentiated and inflammatory natures of CAA in breast cancer microenvironment. Additionally, we propose a miRNA-based regulatory mechanism underlying the process of acquiring inflammatory phenotypes in CAA.
provenance
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language
English
author
Lee, Jiwoo
Hong, Bok Sil
Ryu, Han Suk
Lee, Han-Byoel
Lee, Minju
Park, In Ae
Kim, Jisun
Han, Wonshik
Noh, Dong-Young
Moon, Hyeong-Gon
orcid
Moon, Hyeong-Gon/0000-0002-9981-0286
accessioned
2018-09-28T16:08:09Z
available
2018-09-28T16:08:09Z
issued
2017
citation
PLOS ONE(12): 3
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486457.do
Funder
보건복지부
Funding Program
첨단의료기술개발
Project ID
1465024812
Jurisdiction
Rep.of Korea
Project Name
Development of hormone receptor positive breast cancer personalized medical system using PDX model
rights
openAccess
type
article


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