BACKGROUND: Liver metastasis is associated with a proinflammatory microenvironment and up-regulation of cell adhesion molecules expressed by endothelial cells. The aim of this study was to characterize the interrelations between breast cancer cell-secreted cytokines, macrophages and E-selectin-mediated cancer cell adhesion and their role in metastasis of breast cancer. MATERIALS AND METHODS: Three metastatic breast cancer cell lines (1590, KM22, ZE) were studied. Cell culture supernatants were screened for cytokines and the potential for cytokines to increase tumor-necrosis factor-α (TNF-α) production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell adhesion of fluorescence labelled tumor cells was evaluated by measurement of fluorescence intensity with and without E-selectin-blocking strategies (monoclonal antibodies, cimetidine). RESULTS: Tumor-specific cytokine secretion patterns were revealed. TNF-α secretion from cultured macrophages increased after incubation with tumor supernatants. Tumor cell adhesion was significantly inhibited by cimetidine and monoclonal antibodies against E-selectin (KM22 with cimetidine, p<0.05). CONCLUSION: Breast cancer cell-secreted cytokines stimulate macrophages to produce TNF-α, a known up-regulator of E-selectin expression, and therefore cell adherence to endothelium. Inhibition of this mechanism could be an attractive therapeutic option for the prevention of breast cnacer metastasis.
BACKGROUND:Liver metastasis is associated with a proinflammatory microenvironment and up-regulation of cell adhesion molecules expressed by endothelial cells. The aim of this study was to characterize the interrelations between breast cancer cell-secreted cytokines, macrophages and E-selectin-mediated cancer cell adhesion and their role in metastasis of breast cancer. MATERIALS AND METHODS: Three metastatic breast cancer cell lines (1590, KM22, ZE) were studied. Cell culture supernatants were screened for cytokines and the potential for cytokines to increase tumor-necrosis factor-α (TNF-α) production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell adhesion of fluorescence labelled tumor cells was evaluated by measurement of fluorescence intensity with and without E-selectin-blocking strategies (monoclonal antibodies, cimetidine). RESULTS:Tumor-specific cytokine secretion patterns were revealed. TNF-α secretion from cultured macrophages increased after incubation with tumor supernatants. Tumor cell adhesion was significantly inhibited by cimetidine and monoclonal antibodies against E-selectin (KM22 with cimetidine, p<0.05). CONCLUSION:Breast cancer cell-secreted cytokines stimulate macrophages to produce TNF-α, a known up-regulator of E-selectin expression, and therefore cell adherence to endothelium. Inhibition of this mechanism could be an attractive therapeutic option for the prevention of breast cnacer metastasis.
Authors: Anna Rita Cantelmo; Lena-Christin Conradi; Aleksandra Brajic; Jermaine Goveia; Joanna Kalucka; Andreas Pircher; Pallavi Chaturvedi; Johanna Hol; Bernard Thienpont; Laure-Anne Teuwen; Sandra Schoors; Bram Boeckx; Joris Vriens; Anna Kuchnio; Koen Veys; Bert Cruys; Lise Finotto; Lucas Treps; Tor Espen Stav-Noraas; Francesco Bifari; Peter Stapor; Ilaria Decimo; Kim Kampen; Katrien De Bock; Guttorm Haraldsen; Luc Schoonjans; Ton Rabelink; Guy Eelen; Bart Ghesquière; Jalees Rehman; Diether Lambrechts; Asrar B Malik; Mieke Dewerchin; Peter Carmeliet Journal: Cancer Cell Date: 2016-11-17 Impact factor: 31.743
Authors: Anja K Wege; Marcus Schmidt; Elke Ueberham; Marvin Ponnath; Olaf Ortmann; Gero Brockhoff; Jörg Lehmann Journal: MAbs Date: 2014-05-08 Impact factor: 5.857
Authors: Jodie M Fleming; Tyler C Miller; Michal Kidacki; Erika Ginsburg; Christina H Stuelten; Delisha A Stewart; Melissa A Troester; Barbara K Vonderhaar Journal: Breast Cancer Res Date: 2012-06-25 Impact factor: 6.466