In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation.
Animals
Cell Adhesion
Cell Line, Tumor
Cell Movement
Cell Survival
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mice
Mutation
Neoplasm Transplantation
Nerve Tissue Proteins
/ genetics
Ovarian Neoplasms
/ genetics
Peritoneal Neoplasms
/ genetics
Tumor Suppressor Protein p53
/ genetics
Up-Regulation
AMIGO2
Intra-peritoneal metastasis
Invasion]
Multi-cellular aggregate
Ovarian cancer
Spheroid
Tumorsphere [deleted adhesion
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
10 04 2021
10 04 2021
Historique:
received:
11
11
2020
revised:
06
01
2021
accepted:
23
01
2021
pubmed:
2
2
2021
medline:
6
8
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
The majority of women with ovarian cancer are diagnosed with metastatic disease, therefore elucidating molecular events that contribute to successful metastatic dissemination may identify additional targets for therapeutic intervention and thereby positively impact survival. Using two human high grade serous ovarian cancer cell lines with inactive TP53 and multiple rounds of serial in vivo passaging, we generated sublines with significantly accelerated intra-peritoneal (IP) growth. Comparative analysis of the parental and IP sublines identified a common panel of differentially expressed genes. The most highly differentially expressed gene, upregulated by 60-65-fold in IP-selected sublines, was the type I transmembrane protein AMIGO2. As the role of AMIGO2 in ovarian cancer metastasis remains unexplored, CRISPR/Cas9 was used to reduce AMIGO2 expression, followed by in vitro and in vivo functional analyses. Knockdown of AMIGO2 modified the sphere-forming potential of ovarian cancer cells, reduced adhesion and invasion in vitro, and significantly attenuated IP metastasis. These data highlight AMIGO2 as a new target for a novel anti-metastatic therapeutic approach aimed at blocking cohesion, survival, and adhesion of metastatic tumorspheres.
Identifiants
pubmed: 33524500
pii: S0304-3835(21)00048-3
doi: 10.1016/j.canlet.2021.01.024
pmc: PMC7981259
mid: NIHMS1671215
pii:
doi:
Substances chimiques
AMIGO2 protein, human
0
Nerve Tissue Proteins
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
163-173Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM075762
Pays : United States
Organisme : NIA NIH HHS
ID : F99 AG068527
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA218305
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194697
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA109545
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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