Evidence map›Paper›PMID 36795484›Full record

ArticleJCI insight2023

Cancer-associated mesothelial cell-derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis.

Preety Bajwa, Kasjusz Kordylewicz, Agnes Bilecz, Ricardo R Lastra, Kristen Wroblewski, Yuval Rinkevich, Ernst Lengyel, Hilary A Kenny

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Preety BajwaDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology.
Kasjusz KordylewiczDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology.
Agnes BileczDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology.
Ricardo R LastraDepartment of Pathology, and.
Kristen WroblewskiDepartment of Public Health Sciences, University of Chicago, Chicago, Illinois, USA.
Yuval RinkevichInstitute of Regenerative Biology and Medicine, Helmholtz Zentrum München, Munich, Germany.
Ernst LengyelDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology.
Hilary A KennyDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology.
Gynecologic Oncology Group · USChicago Department of Public Health · USHelmholtz Zentrum München · DE

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI KUNLE ODUNSI · 1985 to 2026
$122.1M
Metabolic reprogramming of the tumor microenvironment and therapy resistanceR35CA264619 · NCI · UNIVERSITY OF CHICAGO · PI Ernst Lengyel · 2021 to 2026
$5.2M
Nicotinamide N-Methyltransferase (NNMT) as a master regulator of cancer stromaR01CA211916 · NCI · UNIVERSITY OF CHICAGO · PI LENGYEL, ERNST · 2017 to 2021
$1.9M
NCI NIH HHS P30 CA014599NCI NIH HHS R01 CA211916NCI NIH HHS R35 CA264619
6 · The paper itself

Abstract

Ovarian cancer (OvCa) preferentially metastasizes in association with mesothelial cell-lined surfaces. We sought to determine if mesothelial cells are required for OvCa metastasis and detect alterations in mesothelial cell gene expression and cytokine secretion upon interaction with OvCa cells. Using omental samples from patients with high-grade serous OvCa and mouse models with Wt1-driven GFP-expressing mesothelial cells, we validated the intratumoral localization of mesothelial cells during human and mouse OvCa omental metastasis. Removing mesothelial cells ex vivo from human and mouse omenta or in vivo using diphtheria toxin-mediated ablation in Msln-Cre mice significantly inhibited OvCa cell adhesion and colonization. Human ascites induced angiopoietin-like 4 (ANGPTL4) and stanniocalcin 1 (STC1) expression and secretion by mesothelial cells. Inhibition of STC1 or ANGPTL4 via RNAi obstructed OvCa cell-induced mesothelial cell to mesenchymal transition while inhibition of ANGPTL4 alone obstructed OvCa cell-induced mesothelial cell migration and glycolysis. Inhibition of mesothelial cell ANGPTL4 secretion via RNAi prevented mesothelial cell-induced monocyte migration, endothelial cell vessel formation, and OvCa cell adhesion, migration, and proliferation. In contrast, inhibition of mesothelial cell STC1 secretion via RNAi prevented mesothelial cell-induced endothelial cell vessel formation and OvCa cell adhesion, migration, proliferation, and invasion. Additionally, blocking ANPTL4 function with Abs reduced the ex vivo colonization of 3 different OvCa cell lines on human omental tissue explants and in vivo colonization of ID8p53-/-Brca2-/- cells on mouse omenta. These findings indicate that mesothelial cells are important to the initial stages of OvCa metastasis and that the crosstalk between mesothelial cells and the tumor microenvironment promotes OvCa metastasis through the secretion of ANGPTL4.

Indexed as

Ovarian NeoplasmsPeritoneal NeoplasmsAngiopoietin-Like Protein 4AnimalsAscitesCell Line, TumorFemaleGlycoproteinsHumansMiceTumor MicroenvironmentAngiopoietin-Like Protein 4ANGPTL4 protein, humanGlycoproteinsteleocalcinCancerCell BiologyMouse modelsObstetrics/gynecologyOncology

Identifiers

PMID36795484
PMCPMC10070116
OpenAlexW4321004607

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.