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Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages

Krawczyk, Krzysztof M. LU ; Nilsson, Helén LU ; Allaoui, Roni LU ; Lindgren, David LU ; Arvidsson, Michael; Leandersson, Karin LU and Johansson, Martin E. LU (2017) In Laboratory Investigation 97(11). p.1296-1305
Abstract

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction... (More)

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction between pRCC tumor and myeloid cells, we established primary cultures from pRCC tissue. We show that human pRCC cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors attract primary human monocytes in vitro. RNAseq data from The Cancer Genome Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned medium from pRCC cultures induced a shift in human monocytes toward the M2 macrophage phenotype. In extended cultures, these macrophages became enlarged and loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These results show for the first time that pRCC primary tumor cells secrete factors that attract and differentiate monocytes into anti-inflammatory tumor-associated macrophages with foam cell histology.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
renal cell carcinoma, IL-8, cancer micorenviroment , CXCL16
in
Laboratory Investigation
volume
97
issue
11
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85032475198
  • pmid:28759013
  • wos:000414046300004
ISSN
0023-6837
DOI
10.1038/labinvest.2017.78
language
English
LU publication?
yes
id
5a6d2359-b32b-4103-8fa4-62c1bec1781e
date added to LUP
2017-11-12 15:56:47
date last changed
2018-02-07 15:04:05
@article{5a6d2359-b32b-4103-8fa4-62c1bec1781e,
  abstract     = {<p>Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction between pRCC tumor and myeloid cells, we established primary cultures from pRCC tissue. We show that human pRCC cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors attract primary human monocytes in vitro. RNAseq data from The Cancer Genome Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned medium from pRCC cultures induced a shift in human monocytes toward the M2 macrophage phenotype. In extended cultures, these macrophages became enlarged and loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These results show for the first time that pRCC primary tumor cells secrete factors that attract and differentiate monocytes into anti-inflammatory tumor-associated macrophages with foam cell histology.</p>},
  author       = {Krawczyk, Krzysztof M. and Nilsson, Helén and Allaoui, Roni and Lindgren, David and Arvidsson, Michael and Leandersson, Karin and Johansson, Martin E.},
  issn         = {0023-6837},
  keyword      = {renal cell carcinoma,IL-8,cancer micorenviroment ,CXCL16},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {1296--1305},
  publisher    = {Nature Publishing Group},
  series       = {Laboratory Investigation},
  title        = {Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages},
  url          = {http://dx.doi.org/10.1038/labinvest.2017.78},
  volume       = {97},
  year         = {2017},
}