Abstract 539: The expression of monocyte/macrophage-restricted scavenger receptor CD163 by malignant cells may be a consequence of cell fusion with tumor-associated macrophages: A novel target for cancer therapy

Abstract

Abstract Solid tumors contain large a number of infiltrating macrophages, which are believed to play a key role in progression and metastasis. Recent research has indicated that malignant cells at times express molecular pathways normally only observed in myeloid cells such as macrophages, hence suggesting that macrophages may fuse with tumor cells. In the present work, we aimed to investigate tumor cell expression of the monocyte/macrophage-restricted scavenger receptor CD163. Initially, the tumor expression of CD163 was examined using a bladder cancer tissue microarray (TMA) containing 425 cores of tumor tissue from 425 patients and 43 paired metastatic lymph nodes. Tumor cells showed a characteristic pleomorphic and atypical morphology with large nuclei, and they were easily distinguished from macrophages. Immunohistochemical staining revealed that CD163-expressing tumor cells could be detected in 98% of the tumor cores, and CD163-expressing metastatic cells could be identified in 77% of the cores of lymph node biopsies. Quantitative real-time polymerase chain reaction and flow cytometric analysis showed that bladder cancer cell lines did not express CD163; however, when co-cultured with macrophages a significant induction of CD163 expression was observed. Utilizing the xCELLigence Real-Time Cell Analyzer System we showed that macrophage-tumor hybrid cells exhibited a significantly increased migratory capacity compared to non-hybrid tumor cells. Tracing the Y chromosome in co-cultures of male macrophages and female T24 cells, we found T24 cell nuclei to be fused with the macrophages. A Cre-inducible mouse model of melanoma expressing a fluorescent reporter system (GFP) was used to characterize hybrid cell formation of macrophages with GFP positive tumors cells in vivo. Flow cytometric analysis demonstrated that >90% of the murine GFP positive tumor cells co-expressed CD163. In conclusion, we show that the expression of the monocyte/macrophage scavenger receptor CD163 was not confined to tumor-associated macrophages. In fact, a significant portion of the tumor cells also expressed CD163, possibly as a result of heterotypic cell fusion between tumor cells and macrophages. Our findings identify CD163 as a possible target for novel cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 539. doi:10.1158/1538-7445.AM2011-539