Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment.
Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells.
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Sara M
SM
Elkashef
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, U.K.
Simon J
SJ
Allison
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Maria
M
Sadiq
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Haneen A
HA
Basheer
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Goreti
G
Ribeiro Morais
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Paul M
PM
Loadman
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Klaus
K
Pors
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, U.K.
Robert A
RA
Falconer
D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D012794:Sialic Acids / Q000032:analysis*
D012794:Sialic Acids; C021319:polysialic acid