Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Establishment of prostate tumor growth and metastasis is supported by bone marrow cells and is mediated by pip5k1α lipid kinase

Karlsson, Richard LU ; Larsson, Per ; Miftakhova, Regina LU ; Khaja, Azharuddin Sajid Syed LU ; Sarwar, Martuza LU ; Semenas, Julius LU ; Chen, Sa ; Hedblom, Andreas LU ; Wang, Tianyan and Ekström-Holka, Kristina LU , et al. (2020) In Cancers 12(9).
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bone marrow cells, PIP5K1α, Prostate cancer metastasis, Therapeutic interventions
in
Cancers
volume
12
issue
9
article number
2719
pages
19 pages
publisher
MDPI AG
external identifiers
  • pmid:32971916
  • scopus:85091205597
ISSN
2072-6694
DOI
10.3390/cancers12092719
language
English
LU publication?
yes
id
3df7a21f-8353-4592-8bc6-4cac80f950ec
date added to LUP
2020-10-27 11:55:11
date last changed
2024-03-20 18:06:36
@article{3df7a21f-8353-4592-8bc6-4cac80f950ec,
  abstract     = {{<p>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.</p>}},
  author       = {{Karlsson, Richard and Larsson, Per and Miftakhova, Regina and Khaja, Azharuddin Sajid Syed and Sarwar, Martuza and Semenas, Julius and Chen, Sa and Hedblom, Andreas and Wang, Tianyan and Ekström-Holka, Kristina and Simoulis, Athanasios and Kumar, Anjani and Ødum, Niels and Grundström, Thomas and Persson, Jenny L.}},
  issn         = {{2072-6694}},
  keywords     = {{Bone marrow cells; PIP5K1α; Prostate cancer metastasis; Therapeutic interventions}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Establishment of prostate tumor growth and metastasis is supported by bone marrow cells and is mediated by pip5k1α lipid kinase}},
  url          = {{http://dx.doi.org/10.3390/cancers12092719}},
  doi          = {{10.3390/cancers12092719}},
  volume       = {{12}},
  year         = {{2020}},
}