PMID- 25721605
OWN - NLM
STAT- MEDLINE
DCOM- 20151204
LR  - 20150321
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 150
IP  - 2
DP  - 2015 Apr
TI  - Cancer-mediated adipose reversion promotes cancer cell migration via IL-6 and 
      MCP-1.
PG  - 255-63
LID - 10.1007/s10549-015-3318-2 [doi]
AB  - The objective of this study is to investigate interactions between adipocytes and 
      breast cancer cells, and identify the responsible factors for the observed 
      effects. In 27 breast cancer patients undergoing mastectomy, mammary adipose 
      tissue was obtained from the breast quadrant bearing the tumor and corresponding 
      non-tumoral quadrant. Isolated normal breast adipocytes (NBAs) and 
      cancer-associated adipocytes (CAAs) were cultured in collagen gels to mimic the 
      in vivo environment. Immunohistochemistry, qRT-PCR, and cell proliferation assays 
      were performed to analyze adipocyte phenotypes. MCF7 and MDA-MB-231 breast cancer 
      cell lines were co-cultured with adipocytes to detect phenotypic changes. 
      Migration of MCF7 and MDA-MB-231 cells was assessed in NBA- and CAA-conditioned 
      media. Cytokine levels in conditioned media were measured by cytokine array. 
      Migration assays were repeated using conditioned media containing neutralizing 
      antibodies. NBAs and CAAs lost their morphological phenotype in culture, 
      acquiring a spindle-like shape, and CAAs showed higher cell proliferation, 
      suggesting reversion to an immature phenotype. In co-cultures with MCF7 or 
      MDA-MB-231 cells, NBAs exhibited increased cell proliferation, indicating 
      acquisition of the immature phenotype of CAAs. MCF7 and MDA-MB-231 showed higher 
      migration in a CAA-conditioned medium than in an NBA-conditioned medium. Cytokine 
      array analysis of conditioned media revealed higher levels of interleukin-6 
      (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in the CAA-conditioned 
      medium. Neutralization experiments using antibodies against IL-6 or MCP-1 showed 
      abrogation of migration-enhancing effects of the CAA-conditioned medium. 
      Adipocytes revert to an immature and proliferative phenotype in the presence of 
      breast cancer cells, and promote cancer cell migration via adipokines including 
      IL-6 and MCP-1.
FAU - Fujisaki, Kaoru
AU  - Fujisaki K
AD  - Department of General Surgery, Chiba University Graduate School of Medicine, 
      1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan.
FAU - Fujimoto, Hiroshi
AU  - Fujimoto H
FAU - Sangai, Takafumi
AU  - Sangai T
FAU - Nagashima, Takeshi
AU  - Nagashima T
FAU - Sakakibara, Masahiro
AU  - Sakakibara M
FAU - Shiina, Nobumitsu
AU  - Shiina N
FAU - Kuroda, Masayuki
AU  - Kuroda M
FAU - Aoyagi, Yasuyuki
AU  - Aoyagi Y
FAU - Miyazaki, Masaru
AU  - Miyazaki M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150227
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Adipocytes/physiology
MH  - Breast Neoplasms/*pathology
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - Cell Shape
MH  - Chemokine CCL2/*physiology
MH  - Coculture Techniques
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - Humans
MH  - Interleukin-6/*physiology
MH  - MCF-7 Cells
EDAT- 2015/02/28 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/02/28 06:00
PHST- 2014/12/15 00:00 [received]
PHST- 2015/02/19 00:00 [accepted]
PHST- 2015/02/28 06:00 [entrez]
PHST- 2015/02/28 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1007/s10549-015-3318-2 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2015 Apr;150(2):255-63. doi: 10.1007/s10549-015-3318-2. 
      Epub 2015 Feb 27.