Tumor growth and progression are linked to an altered lipid metabolism in the tumor microenvironment (TME), including tumor cells and tumor-associated macrophages (TAMs). A growing number of lipid... Show moreTumor growth and progression are linked to an altered lipid metabolism in the tumor microenvironment (TME), including tumor cells and tumor-associated macrophages (TAMs). A growing number of lipid metabolism targeting drugs have shown efficacy in anti-tumor therapy. In addition, exogenously applied lipids and lipid analogues have demonstrated anti-tumor activities in several cancers, including breast cancer. In this study, we investigated the anti-tumor efficacies of the natural lipids palmitic acid (PA), sphingomyelin (SM), ceramide (Cer) and docosahexaenoic acid (DHA) on breast cancer cells. All tested lipids reduced the malignancy of breast cancer cells in vitro by impairing cell proliferation, migration and invasiveness. PA showed superior anti-tumor properties, as it additionally impaired cancer cell viability by inducing apoptosis, without affecting healthy cells. Co-culture experiments further demonstrated that Cer and PA reduced the immunosuppressive phenotype of M2 macrophages and the M2 macrophage-promoted the epithelial-mesenchymal transition (EMT) and migration of breast cancer cells. At the molecular level, this coincided with the up-regulation of E-cadherin. Our results highlight a powerful role for exogenously applied PA and Cer in reducing breast cancer tumorigenicity by simultaneously targeting cancer cells and M2 macrophages. Our findings support the notion that lipids represent alternative biocompatible therapeutic agents for breast cancer. Show less
The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor... Show moreThe macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (N= 78) and healthy donors (N= 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS,p= 0.035) as well as disease-free survival (DFS,p= 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (p= 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (p= 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression. Show less
