Expression of cell surface adhesion molecules on the epithelium of Organ-cultured skin.
Human neonatal foreskin was maintained in organ culture under serum-free, growth-factor-free conditions or in the presence of a combination of growth factors that are known to stimulate keratinocyte proliferation in monolayer culture. Previously, we have shown that normal histology is maintained when growth-factor-free conditions are used but that the epithelium undergoes a hyperproliferative response and invades the dermis in the presence of the exogenous growth factors. In the present study, the tissue was examined by immunofluorescence for expression of alpha 6 and beta 4 integrin components and for E-cadherin. Under growth factor-free conditions, both alpha 6 and beta 4 were localized to the basal surface of epithelial cells in contact with the basement membrane. In contrast, both epitopes were diffusely distributed throughout the basal epithelium in the presence of growth factors. E-cadherin expression was rapidly lost from the tissue in organ culture. This occurred in both the presence and absence of exogenous growth factors. On the basis of these immunochemical results, we conclude that the same changes in alpha 6 and beta 4 expression that are seen in rapidly proliferating keratinocytes and squamous epithelial cell tumors can be seen in the epidermis of organ-cultured skin when it is maintained in the presence of epithelial growth factors. The observed loss of E-cadherin, in contrast, appears to be a consequence of incubation in organ culture.
Varani
J
J
Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
Trinh
D
D
Carey
T E
TE
Liebert
M
M
Wheelock
M J
MJ
D015703:Antigens, CD / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002455:Cell Division; D002462:Cell Membrane / Q000502:physiology; D017077:Culture Media, Conditioned; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D039503:Integrin alpha6; D039663:Integrin beta4; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D009924:Organ Culture Techniques; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D006133:Growth Substances; D039503:Integrin alpha6; D039663:Integrin beta4