Expression of syndecan-1 is induced by differentiation and suppressed by malignant transformation of human keratinocytes.
Syndecans comprise a family of integral membrane proteoglycans that presumably participate in cell-matrix interactions and the modulation of growth factor response. Expression of syndecan-1, a cell surface proteoglycan that binds basic fibroblast growth factor (bFGF) and extracellular matrix components, was studied in cultured human keratinocytes from the oral mucosa and in tissue sections derived from various epithelia and carcinomas of the head and neck. For the study, polyclonal antibodies were raised against the core protein of human syndecan-1. The affinity-purified antibody (designated anti-P117) was shown to react specifically with syndecan-1. Abundant expression of syndecan-1 was detected in frozen sections of various stratified epithelia as well as in cultured keratinocytes. Keratinocytes located in the spinous cell layers showed intense immunoreactivity for syndecan-1, while basal cells stained rather weakly, suggesting that the expression of syndecan-1 could be stimulated during the differentiation of keratinocytes. Cultured human keratinocytes were induced to terminally differentiate by increasing the extracellular calcium concentration of the medium. Parallel to the induction of involucrin expression, the mRNA levels of syndecan-1 were found to increase, suggesting that syndecan-1 is indeed induced during keratinocyte differentiation. The molecular mass and glycosaminoglycan composition of syndecan-1 did not change markedly during calcium-induced differentiation. Malignant transformation was associated with marked reduction of syndecan-1 expression, based on the immunoreactivity of anti-P117 in frozen sections from squamous cell carcinomas (SCCs) of the head and neck.(ABSTRACT TRUNCATED AT 250 WORDS)
Inki
P
P
Department of Medical Biochemistry, University of Turku, Finland.
Larjava
H
H
Haapasalmi
K
K
Miettinen
H M
HM
Grenman
R
R
Jalkanen
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001940:Breast / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D007106:Immune Sera / Q000276:immunology; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011498:Protein Precursors / Q000032:analysis / Q000276:immunology / Q000502:physiology; D011509:Proteoglycans / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D007106:Immune Sera; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; C032253:involucrin; D002118:Calcium