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. 2014 Feb 4;110(3):686-94.
doi: 10.1038/bjc.2013.755. Epub 2013 Dec 10.

Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated macrophages and chemokine/chemoreceptor expression

L Wyler  1 , C U Napoli  2 , B Ingold  1 , T Sulser  3 , M Heikenwälder  4 , P Schraml  1 , H Moch  1
Affiliations

Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated macrophages and chemokine/chemoreceptor expression

L Wyler et al. Br J Cancer. .

Abstract

Background: The mechanisms of brain metastasis in renal cell cancer (RCC) patients are poorly understood. Chemokine and chemokine receptor expression may contribute to the predilection of RCC for brain metastasis by recruitment of monocytes/macrophages and by control or induction of vascular permeability of the blood-brain barrier.

Methods: Frequency and patterns of brain metastasis were determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4, CCL7 (MCP-3), CCR2 and CD68(+) tumour-associated macrophages (TAMs) were analysed in a separate series of 333 primary RCC and in 48 brain metastases using immunohistochemistry.

Results: Fifteen percent of 246 patients with metastasising RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7 expression (75%) in cancer cells of brain metastases was more frequent compared with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density of CD68(+) TAMs was similar in primary RCC and brain metastases. However, TAMs were more frequently CCR2-positive in brain metastases than in primary RCC (P<0.001).

Conclusion: Our data demonstrate that the monocyte-specific chemokine CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that monocyte recruitment by CCR2 contributes to brain metastasis of RCC.

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Figures

Figure 1
Figure 1
Schematic flow with total numbers of RCC, metastasising RCC and brain metastasis RCC in 40′042 autopsies performed at the University of Basel.
Figure 2
Figure 2
Moderate and strong expression of CXCR4 (A, B) and CCL7 (C) in RCC. Upper panel: TMA spots (magnification × 4); lower panel: magnified spot areas ( × 40).
Figure 3
Figure 3
Expression frequencies of CXCR4 (A) and CCL7 (B) in primary RCC and RCC brain metastasis. Data of matched paired primary and brain metastasis RCC are shown on the right side. p-RCC: primary RCC; bm-RCC: brain metastasis RCC. Negative, moderate and strong expression levels are indicated with (−), (+) and (++), respectively.
Figure 4
Figure 4
Infiltration density of CD68 (A) and CCR2 (B) positive tumour-associated macrophages in primary RCC and RCC brain metastasis. p-RCC: primary RCC; bm-RCC: brain metastasis RCC. No, sparse, loose and dense infiltrates of TAMs are indicated with (−), (+), (++) and (+++), respectively. (C) Expression frequency of CCR2 in tumour cells of primary RCC and RCC brain metastasis. Negative, moderate and strong expression levels are indicated with (−), (+) and (++), respectively. Data of matched paired primary and brain metastasis RCC are shown on the right side.
Figure 5
Figure 5
Dense infiltration of CD68- and CCR2-positive tumour-associated macrophages in RCC (A, B (tumour CCR2-negative)); moderate and strong expression of CCR2 (C) in RCC cells. Upper panel: TMA spots (magnification × 4); lower panel: magnified spot areas ( × 40).
See this image and copyright information in PMC

References

    1. Andre F, Cabioglu N, Assi H, Sabourin JC, Delaloge S, Sahin A, Broglio K, Spano JP, Combadiere C, Bucana C, Soria JC, Cristofanilli M. Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol. 2006;17 (6:945–951. - PubMed
    1. Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P, Menon M, Montorsi F, Karakiewicz PI. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol. 2012;23 (4:973–980. - PubMed
    1. Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31 (5:578–583. - PubMed
    1. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30 (7:1073–1081. - PubMed
    1. Culine S, Bekradda M, Kramar A, Rey A, Escudier B, Droz JP. Prognostic factors for survival in patients with brain metastases from renal cell carcinoma. Cancer. 1998;83 (12:2548–2553. - PubMed

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