Evidence map›Paper›PMID 39964754›Full record

ArticleJCI insight2025

Complement activation at the interface between adipocytes and cancer cells drives tumor progression.

Andres Valdivia, Ana Maria Isac, Horacio Cardenas, Guangyuan Zhao, Yaqi Zhang, Hao Huang, Jian-Jun Wei, Mauricio Cuello-Fredes, Sumie Kato, Fernán Gómez-Valenzuela and 3 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
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

13 authors.

Andres ValdiviaDepartment of Obstetrics and Gynecology.
Ana Maria IsacDepartment of Obstetrics and Gynecology.
Horacio CardenasDepartment of Obstetrics and Gynecology.
Guangyuan ZhaoDepartment of Obstetrics and Gynecology.
Yaqi ZhangDepartment of Obstetrics and Gynecology.
Hao HuangDepartment of Obstetrics and Gynecology.
Jian-Jun WeiDepartment of Obstetrics and Gynecology.
Mauricio Cuello-FredesDepartment of Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Sumie KatoDepartment of Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Fernán Gómez-ValenzuelaDepartment of Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Francoise GourroncDepartment of Microbiology and Immunology, College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Aloysius KlingelhutzDepartment of Microbiology and Immunology, College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Daniela MateiDepartment of Obstetrics and Gynecology.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
Functional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726k
BLRD VA I01 BX006012NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA060553NCI NIH HHS R50 CA221675
6 · The paper itself

Abstract

The omentum is the primary site of metastasis for ovarian cancer (OC). Interactions between cancer cells and adipocytes drive an invasive and prometastatic phenotype. Here we studied cancer cell-adipocyte crosstalk by using a direct coculture model with immortalized human visceral nondiabetic pre-adipocytes (VNPADs) and OC cells. We demonstrated increased proliferation, invasiveness, and resistance to cisplatin of cocultured compared with monocultured OC cells. RNA sequencing of OC cells from coculture versus monoculture revealed significant transcriptomic changes, identifying over 200 differentially expressed genes common to OVCAR5 and OVCAR8 cell lines. Enriched pathways included PI3K/AKT and complement activation. Lipid transfer into OC cells from adipocytes induced upregulation of complement C3 and C5 proteins. Inhibiting C3 or C5 reversed the invasive phenotype and C3 knockdown reduced tumor progression in vivo. Increased C3 expression was observed in omental implants compared with primary ovarian tumors and C3 secretion was higher in OC ascites from high-BMI versus low-BMI patients. C3 upregulation in OC cells involved activation of the ATF4-mediated integrated stress response (ISR). Overall, adipocyte-cancer cell interactions promoted invasiveness and tumorigenesis via lipid transfer, activating the ISR, and upregulating complement proteins C3 and C5.

Indexed as

AdipocytesComplement ActivationOvarian NeoplasmsAnimalsCell CommunicationCell Line, TumorCell ProliferationCoculture TechniquesComplement C3Disease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMiceNeoplasm InvasivenessOmentumComplement C3Adipose tissueCancerCell biologyOncology

Identifiers

PMID39964754
PMCPMC11949041

What OpenQuestion 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 OpenQuestion graph.