Trop2 is upregulated in the transition to dysplasia in the metaplastic gastric mucosa.

Animals Antigens, Neoplasm / genetics Basic Helix-Loop-Helix Transcription Factors / genetics Cell Adhesion Molecules / genetics Cell Transformation, Neoplastic / genetics Cells, Cultured Disease Models, Animal Gastric Mucosa / metabolism Genes, ras Humans Metaplasia Mice, Transgenic Microfilament Proteins / genetics Organoids Precancerous Conditions / genetics Signal Transduction Stomach Neoplasms / genetics Up-Regulation
CD44 variant 9 SPEM Tacstd2 dysplasia gastric cancer intestinal metaplasia metaplasia

Journal

The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634

Informations de publication

Date de publication:
07 2020
Historique:
received: 24 12 2019
revised: 20 04 2020
accepted: 09 05 2020
pubmed: 21 5 2020
medline: 18 11 2020
entrez: 21 5 2020
Statut: ppublish

Résumé

Intestinal-type gastric adenocarcinoma arises in a field of pre-existing metaplasia. While biomarkers of cancer and metaplasia have been identified, the definition of dysplastic transition as a critical point in the evolution of cancer has remained obscure. We have evaluated Trop2 as a putative marker of the transition from metaplasia to dysplasia in the stomach in multiple mouse models of metaplasia induction and progression. In addition, TROP2 expression was evaluated in human samples by immunostaining tissue microarrays for metaplasia, dysplasia, and gastric cancer. Dysplastic mouse organoids were evaluated in vitro following shRNA knockdown of Trop2 expression. In mouse models, no Trop2 was observed in the normal corpus and Trop2 was not induced in acute models of metaplasia induction with either L635 or DMP-777. In Mist1-Kras mice, Trop2 expression was not observed in metaplasia at 1 month after Kras induction, but was observed in dysplastic glands at 3-4 months after Kras induction. In human tissues, no Trop2 was observed in normal corpus mucosa or SPEM, but Trop2 expression was observed in incomplete intestinal metaplasia, with significantly less expression in complete intestinal metaplasia. Trop2 expression was observed in all dysplastic and 84% of gastric cancer lesions, although expression levels were variable. Dysplastic mouse organoids from Mist1-Kras mice expressed Trop2 strongly. Knockdown of Trop2 with shRNA markedly reduced organoid growth and budding behavior, and induced the upregulation of apical villin expression. We conclude that Trop2 is upregulated in the transition to dysplasia in the stomach and promotes dysplastic cell behaviors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identifiants

DOI: 10.1002/path.5469 PMID: 32432338 PMC: PMC8010636
pubmed: 32432338
doi: 10.1002/path.5469
pmc: PMC8010636
mid: NIHMS1683723
doi:

Substances chimiques

Antigens, Neoplasm 0
Basic Helix-Loop-Helix Transcription Factors 0
Bhlha15 protein, mouse 0
Cell Adhesion Molecules 0
Microfilament Proteins 0
TACSTD2 protein, human 0
TROP2 protein, mouse 0
Vil1 protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

336-347

Subventions

Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA106183
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA244970
Pays : United States
Organisme : BLRD VA
ID : I01 BX000930
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK071590
Pays : United States
Organisme : BLRD VA
ID : IS1 BX003097
Pays : United States
Organisme : Cancer Research UK
ID : 29075
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK101332
Pays : United States

Informations de copyright

© 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Auteurs

Katherine M Riera (KM)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.

Bogun Jang (B)

Department of Pathology, Jeju National University School of Medicine, Jeju, Republic of Korea.

Jimin Min (J)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Joseph T Roland (JT)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Qing Yang (Q)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Institute of Pathogen Biology, School of Basic Medical Sciences, Shandong University, Jinan, PR China.

William T Fesmire (WT)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.

Sophie Camilleri-Broet (S)

Department of Pathology, McGill University, Montreal, Canada.

Lorenzo Ferri (L)

Department of Surgery, McGill University, Montreal, Canada.

Woo H Kim (WH)

Department of Pathology, Seoul National University, Seoul, Republic of Korea.

Eunyoung Choi (E)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nashville VA Medical Center, Nashville, TN, USA.

James R Goldenring (JR)

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nashville VA Medical Center, Nashville, TN, USA.
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
ORCID: 0000-0002-7833-2940

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Molécules d'adhérence cellulaire › Trop2 is upregulated in the transition to...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Transformation cellulaire néoplasique › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Cellules › Cellules cultivées › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse gastrique › Trop2 is upregulated in the transition to...
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questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'estomac › Tumeurs de l'estomac › Trop2 is upregulated in the transition to...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Trop2 is upregulated in the transition to...