Evidence map›Paper›PMID 35033184›Full record

ArticleCancer & metabolism2022

Prostate cancer cell proliferation is influenced by LDL-cholesterol availability and cholesteryl ester turnover.

Nikki L Raftopulos, Tinashe C Washaya, Andreas Niederprüm, Antonia Egert, Mariam F Hakeem-Sanni, Bianca Varney, Atqiya Aishah, Mariya L Georgieva, Ellinor Olsson, Diandra Z Dos Santos and 10 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
–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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  11. A molecular and immunohistochemical study of 37 cases of ovarian Sertoli-Leydig cell tumor.Virchows Archiv : an international journal of pathology · 2025
    Article
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  19. Metabolic adaptations in prostate cancer.British journal of cancer · 2024
    Review
  20. 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

20 authors.

Nikki L Raftopulos *School of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Tinashe C Washaya *School of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Andreas NiederprümSchool of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Antonia EgertSchool of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Mariam F Hakeem-SanniSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Bianca VarneySchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Atqiya AishahSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Mariya L GeorgievaSchool of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Ellinor OlssonSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Diandra Z Dos SantosSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Zeyad D NassarAdelaide Medical School and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, South Australia, Australia.
Blake J CochranSchool of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Shilpa R NagarajanSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Meghna S KakaniSchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Jordan F HastingsThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
David R CroucherThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Kerry-Anne RyeSchool of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Lisa M ButlerAdelaide Medical School and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, South Australia, Australia.
Thomas GrewalSchool of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Andrew J HoySchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. andrew.hoy@sydney.edu.au.ORCID http://orcid.org/0000-0003-3922-1137

Funding

Movember Foundation MRTA3
6 · The paper itself

Abstract

backgroundProstate cancer growth is driven by androgen receptor signaling, and advanced disease is initially treatable by depleting circulating androgens. However, prostate cancer cells inevitably adapt, resulting in disease relapse with incurable castrate-resistant prostate cancer. Androgen deprivation therapy has many side effects, including hypercholesterolemia, and more aggressive and castrate-resistant prostate cancers typically feature cellular accumulation of cholesterol stored in the form of cholesteryl esters. As cholesterol is a key substrate for de novo steroidogenesis in prostate cells, this study hypothesized that castrate-resistant/advanced prostate cancer cell growth is influenced by the availability of extracellular, low-density lipoprotein (LDL)-derived, cholesterol, which is coupled to intracellular cholesteryl ester homeostasis.

methodsC4-2B and PC3 prostate cancer cells were cultured in media supplemented with fetal calf serum (FCS), charcoal-stripped FCS (CS-FCS), lipoprotein-deficient FCS (LPDS), or charcoal-stripped LPDS (CS-LPDS) and analyzed by a variety of biochemical techniques. Cell viability and proliferation were measured by MTT assay and Incucyte, respectively.

resultsReducing lipoprotein availability led to a reduction in cholesteryl ester levels and cell growth in C4-2B and PC3 cells, with concomitant reductions in PI3K/mTOR and p38MAPK signaling. This reduced growth in LPDS-containing media was fully recovered by supplementation of exogenous low-density lipoprotein (LDL), but LDL only partially rescued growth of cells cultured with CS-LPDS. This growth pattern was not associated with changes in androgen receptor signaling but rather increased p38MAPK and MEK1/ERK/MSK1 activation. The ability of LDL supplementation to rescue cell growth required cholesterol esterification as well as cholesteryl ester hydrolysis activity. Further, growth of cells cultured in low androgen levels (CS-FCS) was suppressed when cholesteryl ester hydrolysis was inhibited.

conclusionsOverall, these studies demonstrate that androgen-independent prostate cancer cell growth can be influenced by extracellular lipid levels and LDL-cholesterol availability and that uptake of extracellular cholesterol, through endocytosis of LDL-derived cholesterol and subsequent delivery and storage in the lipid droplet as cholesteryl esters, is required to support prostate cancer cell growth. This provides new insights into the relationship between extracellular cholesterol, intracellular cholesterol metabolism, and prostate cancer cell growth and the potential mechanisms linking hypercholesterolemia and more aggressive prostate cancer.

Indexed as

ACAT1Cell proliferationCholesteryl esterHSLLDLLDL-cholesterolnCEH1Prostate cancer

Identifiers

PMID35033184
PMCPMC8760736

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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.