- Title
- A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells
- Creator
- McGovern, Jacqui A.; Bock, Nathalie; Shafiee, Abbas; Martine, Laure C.; Wagner, Ferdinand; Baldwin, Jeremy G.; Landgraf, Marietta; Lahr, Christoph A.; Meinert, Christoph; Williams, Elizabeth D.; Pollock, Pamela M.; Denham, Jim; Russell, Pamela J.; Risbridger, Gail P.; Clements, Judith A.; Loessner, Daniela; Holzapfel, Boris M.; Hutmacher, Dietmar W.
- Relation
- Communications Biology Vol. 4, Issue 1, no. 1014
- Publisher Link
- http://dx.doi.org/10.1038/s42003-021-02527-x
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2021
- Description
- Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγnull (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ. Bioluminescent imaging, histology, and immunohistochemistry were used to study metastasis of human PC-3 and LNCaP PCa cells from the prostate to tissue-engineered bone. Here we show pre-seeding scaffolds with human osteoblasts increases the human cellular and extracellular matrix content of bone constructs, compared to unseeded scaffolds. The humanized prostate TME showed a trend to decrease metastasis of PC-3 PCa cells to the tissue-engineered bone, but did not affect the metastatic potential of PCa cells to the endogenous murine bones or organs. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to humanized and murine bone. Together this demonstrates the importance of the TME in PCa bone tropism, although further investigations are needed to delineate specific roles of the TME components in this context.
- Subject
- cancer models; tissue engineering; prostate cancer; bone metastatic tropism; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1475089
- Identifier
- uon:49451
- Identifier
- ISSN:2399-3642
- Rights
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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