Journal article
A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells
JA McGovern, N Bock, A Shafiee, LC Martine, F Wagner, JG Baldwin, M Landgraf, CA Lahr, C Meinert, ED Williams, PM Pollock, J Denham, PJ Russell, GP Risbridger, JA Clements, D Loessner, BM Holzapfel, DW Hutmacher
Communications Biology | NATURE PORTFOLIO | Published : 2021
Open access
Abstract
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 th..
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Awarded by Australian Research Council
Funding Acknowledgements
The Australian Prostate Cancer Center-Queensland (APCRC-Q) and Translational Research Institute (TRI) are supported by grants from the Australian Government. Fibrin glue (TISSEELT Fibrin Sealant) was kindly provided by Baxter Healthcare. rhBMP-7 was a generous gift from Olympus Biotech Corporation. The CD44 (H4C4) and Type II Collagen (II-II6B3) antibodies were obtained from the Developmental Studies Hybridoma Bank (DSHB), created by the NIH and maintained at the University of Iowa, Department of Biology. This work was supported by the Australian Research Council (Future Fellowship awarded to DWH), the National Health and Medical Research Council (NHMRC Project Grant 1082313 to BMH and DWH, NHMRC Peter Doherty Fellowship APP1091734 to NB), the Prostate Cancer Foundation of Australia (PCFA, Young Investigator Award (YI10715) to NB), a grant from Worldwide Cancer Research (WWCR 15-11563 to DWH, PR, EDW) an In Vitro Excellence Research grant from J.J. Richards & Sons Pty Ltd to NB, and an Advance Queensland Women's Research Assistance Program (WRAP035-2019RD1) awarded to JAM. The mouse schematic used in Figs. 1, 4, and 5 was sourced from Wikimedia Commons and was adapted to create these Figures52.