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

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 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.

More Than an Adipokine: The Complex Roles of Chemerin Signaling in Cancer

“…This is opposite to the majority of tumors that display decreased chemerin . While there is little information regarding the potential impact of elevated chemerin expression in renal carcinoma, a recent study sheds some light on the matter [107]. pRCC accounts for approximately 20% of all renal cancers.…”

“…A unique feature of pRCC is the focal aggregation of foam cell macrophages inside the papillae. In the study by Krawczyk et al, foamy macrophages were histologically identified in 82% of pRCC tumors and the macrophages expressed cell surface markers CD689 and CD163 that are characteristic of the M2 anti-inflammatory phenotype [107]. The researchers hypothesized that the pRCC cells must secrete factors that recruit monocytes and contribute to their differentiation into foamy macrophages.…”

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies

“…It mainly functions as a scavenger receptor for oxidized low‐density lipoprotein (oxLDL), and as an adhesion molecule for cells expressing CXCR6 . The soluble form of CXCL16 is produced by constitutive or inducible cleavage of the transmembrane form, and this is involved in inducing the homing process of several leukocytes, including monocytes, T‐lymphoid cells, and natural killer (NK) cells …”

“…8,9 The soluble form of CXCL16 is produced by constitutive or inducible cleavage of the transmembrane form, and this is involved in inducing the homing process of several leukocytes, including monocytes, T-lymphoid cells, and natural killer (NK) cells. 7,8,[10][11][12] The maternal-fetal interface expresses a variety of chemokines and their receptors, including CCL1, CCL3, CCL4, CCL9, CXCL6, and CXCL12, which form a complex network that precisely regulates the proliferation and differentiation of trophoblasts. [13][14][15] In addition, chemokines are involved in the recruitment and differentiation of immune cells, processes that are essential to maintain the special immune microenvironment at the maternal-fetal interface.…”

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

“…IL-8 could induce the chondrogenic differentiation of bone marrow mesenchymal stem cells in vivo and in vitro through the PI3k/AKT cell signaling pathway (Yang et al, 2018). The secretion of IL-8, chemerin, and CXCL16, by papillary renal cell carcinoma, promoted the recruitment of monocytes and the differentiation of macrophages with foam cell phenotype (Krawczyk et al, 2017). IL-8 and GM-CSF were required in the differentiation of acute monocytic leukemia induced by CD44 (Delaunay et al, 2008).…”