Samah A Jassam1, Zaynah Maherally1, James R Smith1, Keyoumars Ashkan1, Federico Roncaroli1, Helen L Fillmore1, Geoffrey J Pilkington1. 1. Cellular and Molecular Neuro-oncology Research Group, Brain Tumour Research Centre, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK (S.A.J., Z.M., J.R.S., H.L.F., G.J.P.); Neuro-surgery, King's College Hospital, Denmark Hill, London, UK (K.A.); Institute of Brain Behaviour and Mental Health, The University of Manchester, Manchester, UK (F.R.).
Abstract
BACKGROUND: CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). METHODS: CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. RESULTS: CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. CONCLUSION: This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E.
BACKGROUND:CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). METHODS:CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. RESULTS:CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. CONCLUSION: This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E.
Authors: María Teresa Elola; Mariana Isabel Capurro; María Marcela Barrio; Peter J Coombs; Maureen E Taylor; Kurt Drickamer; José Mordoh Journal: Breast Cancer Res Treat Date: 2006-07-19 Impact factor: 4.872
Authors: Samah A Jassam; Zaynah Maherally; James R Smith; Keyoumars Ashkan; Federico Roncaroli; Helen L Fillmore; Geoffrey J Pilkington Journal: Int J Mol Sci Date: 2017-07-10 Impact factor: 5.923
Authors: Iole Cordone; Serena Masi; Valentina Summa; Mariantonia Carosi; Antonello Vidiri; Alessandra Fabi; Alessia Pasquale; Laura Conti; Immacolata Rosito; Carmine Maria Carapella; Veronica Villani; Andrea Pace Journal: Breast Cancer Res Date: 2017-04-11 Impact factor: 6.466