Evidence map›Paper›PMID 30890157›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming.

Zhe Wang, Hanxue Sun, Jan Provaznik, Thilo Hackert, Margot Zöller

RetractedErratum issuedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 69 citations in OpenAlex.

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  9. Metabolic features of tumor-derived extracellular vesicles: challenges and opportunities.Extracellular vesicles and circulating nucleic acids · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 2 countries.

Zhe WangDepartment of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
Hanxue SunPancreas Section, University Hospital of Surgery, Im Neuenheimer Feld 110, D69120, Heidelberg, Germany.
Jan ProvaznikGene Core Unit, EMBL, Heidelberg, Germany.
Thilo HackertPancreas Section, University Hospital of Surgery, Im Neuenheimer Feld 110, D69120, Heidelberg, Germany.
Margot ZöllerDepartment of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. margot.zoeller@gmx.net.
University Hospital Heidelberg · DEEuropean Molecular Biology Organization · DEFirst Affiliated Hospital of Guangdong Pharmaceutical University · CNHeidelberg University · DE

Funding

Deutsche Krebshilfe 110836National Natural Science Foundation of China (CN) NSFC 81702877
6 · The paper itself

Abstract

backgroundCancer-initiating cell (CIC) exosomes (CIC-TEX) are suggested reprogramming Non-CIC. Mode of message transfer and engagement of CIC-markers being disputed, we elaborated the impact of CD44v6 and Tspan8 on the response of Non-CIC.

methodsNon-metastasizing CD44v6- and Tspan8-knockdown (kd) pancreatic cancer cells served as Non-CIC. CIC-TEX coculture-induced changes were evaluated by deep-sequencing and functional assays. Tumor progression was surveyed during in vivo CIC-TEX treatment.

resultsDeep-sequencing of CIC-TEX-cocultured CD44v6kd-Non-CIC revealed pronounced mRNA changes in signaling, transport, transcription and translation; altered miRNA affected metabolism, signaling and transcription. CIC-TEX coculture-induced changes in Tspan8kd-Non-CIC mostly relied on CIC-TEX-Tspan8 being required for targeting. CIC-TEX transfer supported apoptosis resistance and significantly promoted epithelial mesenchymal transition, migration, invasion and (lymph)angiogenesis of the kd Non-CIC in vitro and in vivo, deep-sequencing allowing individual mRNA and miRNA assignment to altered functions. Importantly, CIC-TEX act as a hub, initiated by CD44v6-dependent RTK, GPCR and integrin activation and involving CD44v6-assisted transcription and RNA processing. Accordingly, a kinase inhibitor hampered CIC-TEX-fostered tumor progression, which was backed by an anti-Tspan8 blockade of CIC-TEX binding.

conclusionsThis in depth report on the in vitro and in vivo impact of CIC-TEX on CD44v6kd and Tspan8kd Non-CIC unravels hub CIC-TEX activity, highlighting a prominent contribution of the CIC-markers CD44v6 to signaling cascade activation, transcription, translation and miRNA processing in Non-CIC and of Tspan8 to CIC-TEX targeting. Blocking CIC-TEX binding/uptake and uptake-initiated target cell activation significantly mitigated the deleterious CIC-TEX impact on CD44v6kd and Tspan8kd Non-CIC.

Indexed as

AnimalsCell Line, TumorCellular ReprogrammingExosomesHeterograftsHumansHyaluronan ReceptorsMiceMice, NudeMicroRNAsNeoplastic Stem CellsPancreatic NeoplasmsRNA, MessengerSignal TransductionCD44v6 antigenHyaluronan ReceptorsMicroRNAsRNA, MessengerCD44v6Exosome biogenesisExosome message transferNon-cancer stem cell reprogrammingPancreatic cancer stem cellsTspan8

Identifiers

PMID30890157
PMCPMC6425561
OpenAlexW2923361621

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.