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Establishment of Prostate Tumor Growth and Metastasis Is Supported by Bone Marrow Cells and Is Mediated by PIP5K1α Lipid Kinase
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Division of Experimental Cancer Research, Department of Translational Medicine, Lund University, Clinical Research Centre, Malmö, Sweden.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Genetics, Kazan Federal University, Kazan, Russia.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0003-1594-1826
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2020 (English)In: Cancers, ISSN 2072-6694, Vol. 12, no 9, article id 2719Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
MDPI, 2020. Vol. 12, no 9, article id 2719
Keywords [en]
prostate cancer metastasis, bone marrow cells, PIP5K1α, therapeutic interventions
National Category
Clinical Laboratory Medicine Cancer and Oncology
Research subject
biomedical laboratory science
Identifiers
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
Projects
tumor microenvironment
Funder
Swedish Cancer Society, CAN2017/381Swedish Research CouncilCancerforskningsfonden i NorrlandAvailable from: 2020-09-30 Created: 2020-09-30 Last updated: 2023-03-24Bibliographically approved

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

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Karlsson, RichardLarsson, PerMiftakhova, Regina R.Khaja, Azharuddin Sajid SyedSemenas, JuliusChen, SaHedblom, AndreasWang, TianyanKumar, AnjaniGrundström, ThomasPersson, Jenny L.
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Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)
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Cancers
Clinical Laboratory MedicineCancer and Oncology

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