Introduction: Infiltrating cells of the tumor microenvironment are important for the growth and spreading of cancer. CD163 is a macrophage-specific hemoglobin scavenger receptor. It is predominantly expressed by alternatively activated macrophages (M2), which is a cell subtype thought to have important tumor-supporting functions. We hypothesized that CD163 mRNA and protein expression may be significant markers of disease severity in bladder cancer. Furthermore, recent findings have indicated that malignant cells express molecular pathways normally only expressed in macrophages, which led us to investigate the possible tumor cell CD163 expression.

Materials and Methods: CD163, IL-6, and IL-10 mRNA expression levels were measured using quantitative real-time polymerase chain reaction (RT-qPCR) in bladder cancer biopsy samples obtained from 87 patients followed for a median of 5.1 years (range, 0.07 to 12.9 years). The subcellular distribution of CD163-positive cells was investigated by immunohistochemistry in a subset of 46 bladder cancer biopsy samples. After co-culturing human monocyte-derived macrophages with T24 bladder cancer cells for 48 hours, the expression of the macrophage scavenger receptor CD163 was examined using flow cytometry.

Results: CD163 mRNA was expressed in all 87 biopsies, and its expression was strongly correlated with overall (p=0.0028) and relapse-free survival (p=0.0003). Moreover, it was significantly increased in invasive (T2-T4) (p=0.017) and aggressive (grade III/IV) cancers (p=0.015). The expression strongly correlated with local expression of IL-6 (r=0.72, p<0.0001) and IL-10 (r=0.75, p<0.0001), mediators known to induce CD163 expression in vitro. An association between the density of CD163 immunohistochemical positive infiltrating cells and histologically advanced bladder cancer, confirmed the mRNA expression findings. Surprisingly, a large fraction of biopsies (39%) showed definite expression of CD163 by the tumor cells, which indicated the possibility of horizontal mRNA transfer or heterotypic cell fusion. RT-qPCR and flow cytometric analysis showed that human bladder cancer cell lines did not express CD163; however, co-culturing bladder cancer cells with macrophages induced significant tumor cell CD163-expression.

Conclusion: In conclusion, we show a strong association between CD163 mRNA expression in bladder cancer biopsies and the severity of the disease, on the one hand, and poor survival on the other hand. CD163 expression was not confined to the infiltrating macrophages. It was also observed in a significant portion of the tumor cells. Our findings identify CD163 as a possible target for novel cancer therapy and underline the importance of the cellular interaction between tumor cells and immune cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1354.