title: Transient P-cadherin expression in radiation proctitis; a model of mucosal injury and repair.
abstract: 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.
authors.affiliation: Department of Surgery, Clinical Research Institute, University of Birmingham, Birmingham, UK. r.g.hardy@bham.ac.uk
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hardy
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brown
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Miller
authors.forename: Chris
authors.initials: C
authors.lastname: Tselepis
authors.forename: Dion G
authors.initials: DG
authors.lastname: Morton
authors.forename: Janusz A Z
authors.initials: JA
authors.lastname: Jankowski
authors.forename: D Scott A
authors.initials: DS
authors.lastname: Sanders
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008954:Models, Biological; D011349:Proctitis / Q000378:metabolism* / Q000473:pathology; D011832:Radiation Injuries / Q000378:metabolism* / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000532:radiotherapy*; D014945:Wound Healing
chemical_list: D015820:Cadherins