Evidence map›Paper›PMID 33023532›Full record

ArticleBMC cancer2020

TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells.

Ruth M Escalona, Maree Bilandzic, Patrick Western, Elif Kadife, George Kannourakis, Jock K Findlay, Nuzhat Ahmed

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

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  13. The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024
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  15. bioRxiv : the preprint server for biology · 2023
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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

7 authors at 3 institutions in 1 country.

Ruth M EscalonaDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, 3050, Australia.
Maree BilandzicCentre for Cancer Research, Hudson Institute of Medical Research, and the Department of Molecular and Translational Science, Monash University, Melbourne, VIC, 3168, Australia.
Patrick WesternCentre for Reproductive Health, Hudson Institute of Medical Research, and the Department of Molecular and Translational Science, Monash University, Melbourne, VIC, 3168, Australia.
Elif KadifeFiona Elsey Cancer Research Institute, Ballarat, 3353, Australia.
George KannourakisFiona Elsey Cancer Research Institute, Ballarat, 3353, Australia.
Jock K FindlayDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, 3050, Australia.
Nuzhat AhmedDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, 3050, Australia. nuzhata@unimelb.edu.au.ORCID http://orcid.org/0000-0001-8379-5053
Federation University · AUHudson Institute of Medical Research · AUThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe metzincin family of metalloproteinases and the tissue inhibitors of metalloproteinases (TIMPs) are essential proteins required for biological processes during cancer progression. This study aimed to determine the role of TIMP-2 in ovarian cancer progression and chemoresistance by reducing TIMP-2 expression in vitro in Fallopian tube secretory epithelial (FT282) and ovarian cancer (JHOS2 and OVCAR4) cell lines.

methodsFT282, JHOS2 and OVCAR4 cells were transiently transfected with either single or pooled TIMP-2 siRNAs. The expression of different genes after TIMP-2 knock down (T2-KD) or in response to chemotherapy was determined at the mRNA level by quantitative real time PCR (qRT-PCR) and at the protein level by immunofluorescence. Sensitivity of the cell lines in response to chemotherapy after TIMP-2 knock down was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Cell invasion in response to TIMP-2 knockdown was determined by xCELLigence.

resultsSixty to 90 % knock down of TIMP-2 expression was confirmed in FT282, OVCAR4 and JHOS2 cell lines at the mRNA and protein levels. TIMP-2 knock down did not change the mRNA expression of TIMP-1 or TIMP-3. However, a significant downregulation of MMP-2 in T2-KD cells occurred at both the protein and activation levels, compared to Control (Cont; scrambled siRNA) and Parental cells (P, transfection reagent only). In contrast, membrane bound MT1-MMP protein levels were significantly upregulated in T2-KD compared to Cont and P cells. T2-KD cells exhibited enhanced proliferation and increased sensitivity to cisplatin and paclitaxel treatments. Enhanced invasion was observed in the T2-KD-JOSH2 and OVCAR4 cells but not in T2-KD-FT282 cells. Treatment with cisplatin or paclitaxel significantly elevated the expression of TIMP-2 in Cont cells but not in T2-KD cells, consistent with significantly elevated expression of chemoresistance and CSC markers and activation of STAT3. Furthermore, a potent inhibitor of STAT3 activation, Momelotinib, suppressed chemotherapy-induced activation of P-STAT3 in OVCAR4 cells with concomitant reductions in the expression of chemoresistance genes and CSC markers.

conclusionsThe above results suggest that TIMP-2 may have a novel role in ovarian cancer proliferation, invasion and chemoresistance.

Indexed as

Antineoplastic Agents, PhytogenicBenzamidesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansNeoplasm InvasivenessNeoplastic Stem CellsOvarian NeoplasmsPaclitaxelProtein Kinase InhibitorsPyrimidinesSTAT3 Transcription FactorTissue Inhibitor of Metalloproteinase-2Antineoplastic Agents, PhytogenicBenzamidesN-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamidePaclitaxelProtein Kinase InhibitorsPyrimidinesSTAT3 protein, humanSTAT3 Transcription FactorTIMP2 protein, humanTissue Inhibitor of Metalloproteinase-2Cancer stem cellsChemosensitivityInvasionMMPsOvarian cancerProliferationSTAT3TIMP-2

Identifiers

PMID33023532
PMCPMC7542139
OpenAlexW3092157046

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.