CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis

  • Int J Mol Sci. 2017 Jul 10;18(7):1474. doi: 10.3390/ijms18071474.
Samah A Jassam  1 ,  Zaynah Maherally  2 ,  James R Smith  3 ,  Keyoumars Ashkan  4 ,  Federico Roncaroli  5 ,  Helen L Fillmore  6 ,  Geoffrey J Pilkington  7
Affiliations
  • 1. Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. [email protected].
  • 2. Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. [email protected].
  • 3. Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. [email protected].
  • 4. Neuro-Surgery, King's College Hospital, Denmark Hill, London SE5 9RS, UK. [email protected].
  • 5. Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, Oxford Road, Manchester M13 9PT, UK. [email protected].
  • 6. Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. [email protected].
  • 7. Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. [email protected].
PMID: 28698503 DOI: 10.3390/ijms18071474
Abstract

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with Cancer metastasis, while expression of E-Selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related Cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary Non-Small Cell Lung Cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of Cancer cell-brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells (p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of Cancer cell-brain endothelium. CD15s immunoblocking significantly decreased Cancer cell adhesion to brain endothelium under static and shear stress conditions (p < 0.001), highlighting the role of CD15s-CD62E interaction in brain metastasis.

Keywords
CD15s; CD62E; Sialyl Lewis X; adhesion; brain metastasis.