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

Autor: Karin Leandersson, Roni Allaoui, David Lindgren, Krzysztof M. Krawczyk, Martin Johansson, Helén Nilsson, Michael Arvidsson
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Chemokine
Nephrectomy
Monocytes
0302 clinical medicine
Tumor Cells
Cultured
Tumor Microenvironment
Cells
Cultured
Foam cell
Receptors
Scavenger
biology
Papillary renal cell carcinomas
Middle Aged
Primary tumor
Kidney Neoplasms
Neoplasm Proteins
Tumor Burden
Chemotaxis
Leukocyte
medicine.anatomical_structure
030220 oncology & carcinogenesis
Intercellular Signaling Peptides and Proteins
Chemokines
Chemokines
CXC
Research Article
medicine.medical_specialty
Pathology and Forensic Medicine
03 medical and health sciences
Internal medicine
medicine
Humans
Interleukin 8
Molecular Biology
Carcinoma
Renal Cell
CXCL16
Aged
Tumor microenvironment
Monocyte
Interleukin-8
Cell Biology
Chemokine CXCL16
medicine.disease
Coculture Techniques
030104 developmental biology
Endocrinology
Culture Media
Conditioned
Cell Transdifferentiation
Cancer research
biology.protein
Neoplasm Grading
Foam Cells
Zdroj: Laboratory Investigation; a Journal of Technical Methods and Pathology
ISSN: 1530-0307
0023-6837
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: