L1CAM is required for early dissemination of fallopian tube carcinoma precursors to the ovary.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
12 12 2022
12 12 2022
Historique:
received:
22
04
2020
accepted:
29
11
2022
entrez:
12
12
2022
pubmed:
13
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Most ovarian high-grade serous carcinomas (HGSC) arise from Serous Tubal Intraepithelial Carcinoma (STIC) lesions in the distal end of the fallopian tube (FT). Formation of STIC lesions from FT secretory cells leads to seeding of the ovarian surface, with rapid tumor dissemination to other abdominal structures thereafter. It remains unclear how nascent malignant cells leave the FT to colonize the ovary. This report provides evidence that the L1 cell adhesion molecule (L1CAM) contributes to the ability of transformed FT secretory cells (FTSEC) to detach from the tube, survive under anchorage-independent conditions, and seed the ovarian surface. L1CAM was highly expressed on the apical cells of STIC lesions and contributed to ovarian colonization by upregulating integrins and fibronectin in malignant cells and activating the AKT and ERK pathways. These changes increased cell survival under ultra-low attachment conditions that mimic transit from the FT to the ovary. To study dissemination to the ovary, we developed a tumor-ovary co-culture model. We showed that L1CAM expression was important for FT cells to invade the ovary as a cohesive group. Our results indicate that in the early stages of HGSC development, transformed FTSECs disseminate from the FT to the ovary in a L1CAM-dependent manner.
Identifiants
pubmed: 36509990
doi: 10.1038/s42003-022-04314-8
pii: 10.1038/s42003-022-04314-8
pmc: PMC9744873
doi:
Substances chimiques
Neural Cell Adhesion Molecule L1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1362Subventions
Organisme : NCI NIH HHS
ID : P50CA228991
Pays : United States
Organisme : NCI NIH HHS
ID : P50CA217685
Pays : United States
Organisme : NCI NIH HHS
ID : F32CA221093
Pays : United States
Informations de copyright
© 2022. The Author(s).
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