Up-regulation of functional chemokine receptor CCR3 in human renal cell carcinoma.

Abstract

There is increasing evidence that chemokines and chemokine receptors are causally involved in tumorigenesis by facilitating tumor proliferation and metastasis. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). We, therefore, analyzed the expression of chemokine receptors in tumor specimens and adjacent healthy kidney tissues [normal kidney cell (NKC)] from 10 RCC patients. We also characterized the permanent RCC cell line A-498. CCR6, CXCR2, and CXCR3 were consistently expressed by both malignant cells and NKCs. A-498 displayed additional expression of CXCR4. Importantly, the expression of CCR3 was almost absent on NKCs but clearly enhanced in a substantial proportion of RCC specimens. The primary CCR3 ligand, eotaxin-1/CCL11, induced intracellular Ca2+ mobilization, receptor internalization, and proliferation in A-498 cells confirming signaling competence of RCC-associated CCR3. In addition, we screened tumor tissue sections of 219 patients and found that 28% (62 of 219) expressed the CCR3 receptor. The presence of CCR3 in tumor samples seemed to correlate with the grade of malignancy. Previous work has established that eotaxin-1 expression is induced by tumor necrosis factor-alpha, a cytokine known to be present in RCC tissue. Our data, therefore, supports a scenario in which eotaxin-1 as part of tumor-associated inflammation promotes progression and dissemination of CCR3-positive RCC.

• Authors: Karin Jöhrer, Claudia Zelle-Rieser, Alexander Perathoner, Patrizia Moser, Martina Hager, Reinhold Ramoner, Hubert Gander, Lorenz Höltl, Georg Bartsch, Richard Greil, Martin Thurnher
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 7 Pg. 2459-65 (Apr 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15814620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL11 protein, human
• CCR3 protein, human
• Chemokine CCL11
• Chemokines, CC
• RNA, Messenger
• Receptors, CCR3
• Receptors, Chemokine
• Calcium

Topics

• Biological Transport
• Calcium (metabolism)
• Carcinoma, Renal Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemokine CCL11
• Chemokines, CC (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kidney Neoplasms (genetics, metabolism, pathology)
• Male
• Neoplasm Staging
• Paraffin Embedding
• RNA, Messenger (genetics, metabolism)
• Receptors, CCR3
• Receptors, Chemokine (genetics, metabolism)
• Tissue Array Analysis
• Up-Regulation (genetics)