Evidence map›Paper›PMID 34396988›Full record

ArticleThe Journal of clinical investigation2021

Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling.

Jin Qian, Bauer L LeSavage, Kelsea M Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T Eggold, Yiren Xiao, Katherine C Fuh, Venkatesh Krishnan, Annika Enejder and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
14.6field-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

84 citing papers in PubMed, 121 citations in OpenAlex.

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  15. Triptolide targetsFrontiers in pharmacology · 2026
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24 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 3 countries.

Jin QianDepartment of Radiation Oncology.
Bauer L LeSavageDepartment of Bioengineering, and.
Kelsea M HubkaDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Chenkai MaMolecular Diagnostics Solutions, CSIRO Health and Biosecurity, North Ryde, New South Wales, Australia.
Suchitra NatarajanDepartment of Radiation Oncology.
Joshua T EggoldDepartment of Radiation Oncology.
Yiren XiaoDepartment of Radiation Oncology.
Katherine C FuhDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University, St. Louis, Missouri, USA.
Venkatesh KrishnanDepartment of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
Annika EnejderDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Sarah C HeilshornDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Oliver DorigoDepartment of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
Erinn B RankinDepartment of Radiation Oncology.
Stanford University · USBioengineering Center · RUCSIRO Health and Biosecurity · AUWashington University in St. Louis · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
NCI NIH HHS T32 CA009302
6 · The paper itself

Abstract

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-β signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCisplatinDrug Resistance, NeoplasmEpitheliumFemaleHumansMiceNeoplastic Stem CellsOrganoidsOsteopontinOvarian NeoplasmsParacrine CommunicationSignal TransductionTumor MicroenvironmentAntineoplastic AgentsCisplatinOsteopontinSPP1 protein, humanSpp1 protein, mouseCancerCytokinesOncologySignal transduction

Identifiers

PMID34396988
PMCPMC8363279
OpenAlexW3193292905

What OpenQuestion holds

Textmetadata
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.