Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Establishment of Prostate Tumor Growth and Metastasis Is Supported by Bone Marrow Cells and Is Mediated by PIP5K1α Lipid Kinase
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Division of Experimental Cancer Research, Department of Translational Medicine, Lund University, Clinical Research Centre, Malmö, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Genetics, Kazan Federal University, Kazan, Russia.
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).ORCID-id: 0000-0003-1594-1826
Visa övriga samt affilieringar
2020 (Engelska)Ingår i: Cancers, ISSN 2072-6694, Vol. 12, nr 9, artikel-id 2719Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Cancer cells facilitate growth and metastasis by using multiple signals from the cancer-associated microenvironment. However, it remains poorly understood whether prostate cancer (PCa) cells may recruit and utilize bone marrow cells for their growth and survival. Furthermore, the regulatory mechanisms underlying interactions between PCa cells and bone marrow cells are obscure. In this study, we isolated bone marrow cells that mainly constituted populations that were positive for CD11b and Gr1 antigens from xenograft PC-3 tumor tissues from athymic nu/nu mice. We found that the tumor-infiltrated cells alone were unable to form tumor spheroids, even with increased amounts and time. By contrast, the tumor-infiltrated cells together with PCa cells formed large numbers of tumor spheroids compared with PCa cells alone. We further utilized xenograft athymic nu/nu mice bearing bone metastatic lesions. We demonstrated that PCa cells were unable to survive and give rise to colony-forming units (CFUs) in media that were used for hematopoietic cell colony-formation unit (CFU) assays. By contrast, PC-3M cells survived when bone marrow cells were present and gave rise to CFUs. Our results showed that PCa cells required bone marrow cells to support their growth and survival and establish bone metastasis in the host environment. We showed that PCa cells that were treated with either siRNA for PIP5K1α or its specific inhibitor, ISA-2011B, were unable to survive and produce tumor spheroids, together with bone marrow cells. Given that the elevated expression of PIP5K1α was specific for PCa cells and was associated with the induced expression of VEGF receptor 2 in PCa cells, our findings suggest that cancer cells may utilize PIP5K1α-mediated receptor signaling to recruit growth factors and ligands from the bone marrow-derived cells. Taken together, our study suggests a new mechanism that enables PCa cells to gain proliferative and invasive advantages within their associated host microenvironment. Therapeutic interventions using PIP5K1α inhibitors may not only inhibit tumor invasion and metastasis but also enhance the host immune system.

Ort, förlag, år, upplaga, sidor
MDPI, 2020. Vol. 12, nr 9, artikel-id 2719
Nyckelord [en]
prostate cancer metastasis, bone marrow cells, PIP5K1α, therapeutic interventions
Nationell ämneskategori
Klinisk laboratoriemedicin Cancer och onkologi
Forskningsämne
biomedicinsk laboratorievetenskap
Identifikatorer
URN: urn:nbn:se:umu:diva-175507DOI: 10.3390/cancers12092719ISI: 000582024400001PubMedID: 32971916Scopus ID: 2-s2.0-85091205597OAI: oai:DiVA.org:umu-175507DiVA, id: diva2:1472092
Projekt
tumor microenvironment
Forskningsfinansiär
Cancerfonden, CAN2017/381VetenskapsrådetCancerforskningsfonden i NorrlandTillgänglig från: 2020-09-30 Skapad: 2020-09-30 Senast uppdaterad: 2023-03-24Bibliografiskt granskad

Open Access i DiVA

fulltext(9645 kB)265 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 9645 kBChecksumma SHA-512
1283859e7be4d613b8d6870a94f7b8463458662184c287dd94027aa32c33fa9f9887809f18384d39768fb498cbf786f92c89885ee0f7ef6da70640c5cf20c6c5
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Karlsson, RichardLarsson, PerMiftakhova, Regina R.Khaja, Azharuddin Sajid SyedSemenas, JuliusChen, SaHedblom, AndreasWang, TianyanKumar, AnjaniGrundström, ThomasPersson, Jenny L.

Sök vidare i DiVA

Av författaren/redaktören
Karlsson, RichardLarsson, PerMiftakhova, Regina R.Khaja, Azharuddin Sajid SyedSemenas, JuliusChen, SaHedblom, AndreasWang, TianyanKumar, AnjaniGrundström, ThomasPersson, Jenny L.
Av organisationen
Institutionen för molekylärbiologi (Medicinska fakulteten)Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
I samma tidskrift
Cancers
Klinisk laboratoriemedicinCancer och onkologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 265 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 589 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf