Morphology at both cellular and glandular levels in the colon is dependent to an extent on cell-cell adhesion mediated by
cadherin-
catenin complexes. Alterations in the expression of
E-cadherin, the
cadherin normally present in colon, have been shown to be implicated in tissue remodelling within the gastrointestinal tract. Furthermore, it has previously been shown that
P-cadherin, normally present only in stratified epithelia and placenta, is expressed in
colitis and during neoplastic change in the colon. The morphological features of mucosal injury induced by pre-operative
radiotherapy in the non-neoplastic rectal mucosa were studied in patients with rectal
adenocarcinoma. Three characteristic phases of radiation
proctitis were defined on histological grounds (acute injury, and early and late regenerative phases) essentially correlating with the time interval between
radiotherapy and surgery; such features were mirrored by alterations in
cadherin-
catenin expression and localization in rectal crypts. On immunohistochemistry and western blotting,
P-cadherin was highly expressed in the acute injury and early regenerative phases, with a decreased level of expression during late regeneration.
E-cadherin and associated
catenins were translocated from membrane to cytoplasm in degenerating crypts, with return of normal membranous expression in regenerating crypts. In conclusion, radiation-induced
proctitis represents an in vivo model of mucosal injury and regeneration and provides a valid model in which to study events during epithelial injury and repair. Altered
cadherin expression, in particular transient aberrant
P-cadherin expression, is intimately associated with these processes.