Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.

Hdl Handle:
http://hdl.handle.net/10147/207683
Title:
Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.
Authors:
Sullivan, Shane; Tosetto, Miriam; Kevans, David; Coss, Alan; Wang, Laimun; O'Donoghue, Diarmuid; Hyland, John; Sheahan, Kieran; Mulcahy, Hugh; O'Sullivan, Jacintha
Affiliation:
Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Dublin,, Ireland.
Citation:
Int J Cancer. 2009 Jul 1;125(1):54-61.
Journal:
International journal of cancer. Journal international du cancer
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207683
DOI:
10.1002/ijc.24275
PubMed ID:
19291794
Abstract:
Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro- and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.
Language:
eng
MeSH:
Adult; Aged; Aged, 80 and over; Blotting, Western; Cathepsin L; Cathepsins/*metabolism; Cell Nucleus/*metabolism/pathology; Colorectal Neoplasms/*metabolism/pathology; Cysteine Endopeptidases/*metabolism; Cytoplasm/*metabolism/pathology; Disease Progression; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate; Tissue Array Analysis; Tumor Cells, Cultured; Tumor Markers, Biological/*metabolism
ISSN:
1097-0215 (Electronic); 0020-7136 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorSullivan, Shaneen_GB
dc.contributor.authorTosetto, Miriamen_GB
dc.contributor.authorKevans, Daviden_GB
dc.contributor.authorCoss, Alanen_GB
dc.contributor.authorWang, Laimunen_GB
dc.contributor.authorO'Donoghue, Diarmuiden_GB
dc.contributor.authorHyland, Johnen_GB
dc.contributor.authorSheahan, Kieranen_GB
dc.contributor.authorMulcahy, Hughen_GB
dc.contributor.authorO'Sullivan, Jacinthaen_GB
dc.date.accessioned2012-02-01T10:34:51Z-
dc.date.available2012-02-01T10:34:51Z-
dc.date.issued2012-02-01T10:34:51Z-
dc.identifier.citationInt J Cancer. 2009 Jul 1;125(1):54-61.en_GB
dc.identifier.issn1097-0215 (Electronic)en_GB
dc.identifier.issn0020-7136 (Linking)en_GB
dc.identifier.pmid19291794en_GB
dc.identifier.doi10.1002/ijc.24275en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207683-
dc.description.abstractPrevious in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro- and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCathepsin Len_GB
dc.subject.meshCathepsins/*metabolismen_GB
dc.subject.meshCell Nucleus/*metabolism/pathologyen_GB
dc.subject.meshColorectal Neoplasms/*metabolism/pathologyen_GB
dc.subject.meshCysteine Endopeptidases/*metabolismen_GB
dc.subject.meshCytoplasm/*metabolism/pathologyen_GB
dc.subject.meshDisease Progressionen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoenzyme Techniquesen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNeoplasm Stagingen_GB
dc.subject.meshPrognosisen_GB
dc.subject.meshSurvival Rateen_GB
dc.subject.meshTissue Array Analysisen_GB
dc.subject.meshTumor Cells, Cultureden_GB
dc.subject.meshTumor Markers, Biological/*metabolismen_GB
dc.titleLocalization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.en_GB
dc.contributor.departmentCentre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Dublin,, Ireland.en_GB
dc.identifier.journalInternational journal of cancer. Journal international du canceren_GB
dc.description.provinceLeinster-

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