Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone

Jacqui A. McGovern, Abbas Shafiee, Ferdinand Wagner, Christoph A. Lahr, Marietta Landgraf, Christoph Meinert, Elizabeth D. Williams, Pamela J. Russell, Judith A. Clements, Daniela Loessner, Boris M. Holzapfel, Gail P. Risbridger, Dietmar W. Hutmacher

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice. The hTEBC formed a physiologically mature organ bone which allowed homing of metastatic PCa cells. Humanization of prostate tissue had no significant effect on the tumor burden at the primary site over the 4 weeks following intraprostatic injection, yet reduced the incidence and burden of metastases in the hTEBC. Spontaneous PCa metastases were detected in the lungs and spleen with no significant differences between the humanized and non-humanized prostate groups. A significantly greater metastatic tumor burden was observed in the liver when metastasis occurred from the humanized prostate. Together, our data suggests that the presence of human-derived CAFs and BVECs in the primary PCa microenvironment influences selectively the metastatic and homing behavior of PC3 cells in this model. Our orthotopic and humanized prostate cancer model developed via convergence of cancer research and tissue engineering concepts provides an important platform to study species-specific PCa bone metastasis and to develop and test therapeutic strategies.

Original languageEnglish
Article number438
Number of pages15
JournalCancers
Volume10
Issue number11
DOIs
Publication statusPublished - 13 Nov 2018

Keywords

  • Bone metastasis
  • Cancer-associated fibroblast
  • Humanized bone
  • Orthotopic model
  • Prostate cancer
  • Tissue engineering
  • Tumor microenvironment

Cite this

McGovern, J. A., Shafiee, A., Wagner, F., Lahr, C. A., Landgraf, M., Meinert, C., ... Hutmacher, D. W. (2018). Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone. Cancers, 10(11), [438]. https://doi.org/10.3390/cancers10110438
McGovern, Jacqui A. ; Shafiee, Abbas ; Wagner, Ferdinand ; Lahr, Christoph A. ; Landgraf, Marietta ; Meinert, Christoph ; Williams, Elizabeth D. ; Russell, Pamela J. ; Clements, Judith A. ; Loessner, Daniela ; Holzapfel, Boris M. ; Risbridger, Gail P. ; Hutmacher, Dietmar W. / Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone. In: Cancers. 2018 ; Vol. 10, No. 11.
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title = "Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone",
abstract = "The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice. The hTEBC formed a physiologically mature organ bone which allowed homing of metastatic PCa cells. Humanization of prostate tissue had no significant effect on the tumor burden at the primary site over the 4 weeks following intraprostatic injection, yet reduced the incidence and burden of metastases in the hTEBC. Spontaneous PCa metastases were detected in the lungs and spleen with no significant differences between the humanized and non-humanized prostate groups. A significantly greater metastatic tumor burden was observed in the liver when metastasis occurred from the humanized prostate. Together, our data suggests that the presence of human-derived CAFs and BVECs in the primary PCa microenvironment influences selectively the metastatic and homing behavior of PC3 cells in this model. Our orthotopic and humanized prostate cancer model developed via convergence of cancer research and tissue engineering concepts provides an important platform to study species-specific PCa bone metastasis and to develop and test therapeutic strategies.",
keywords = "Bone metastasis, Cancer-associated fibroblast, Humanized bone, Orthotopic model, Prostate cancer, Tissue engineering, Tumor microenvironment",
author = "McGovern, {Jacqui A.} and Abbas Shafiee and Ferdinand Wagner and Lahr, {Christoph A.} and Marietta Landgraf and Christoph Meinert and Williams, {Elizabeth D.} and Russell, {Pamela J.} and Clements, {Judith A.} and Daniela Loessner and Holzapfel, {Boris M.} and Risbridger, {Gail P.} and Hutmacher, {Dietmar W.}",
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McGovern, JA, Shafiee, A, Wagner, F, Lahr, CA, Landgraf, M, Meinert, C, Williams, ED, Russell, PJ, Clements, JA, Loessner, D, Holzapfel, BM, Risbridger, GP & Hutmacher, DW 2018, 'Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone', Cancers, vol. 10, no. 11, 438. https://doi.org/10.3390/cancers10110438

Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone. / McGovern, Jacqui A.; Shafiee, Abbas; Wagner, Ferdinand; Lahr, Christoph A.; Landgraf, Marietta; Meinert, Christoph; Williams, Elizabeth D.; Russell, Pamela J.; Clements, Judith A.; Loessner, Daniela; Holzapfel, Boris M.; Risbridger, Gail P.; Hutmacher, Dietmar W.

In: Cancers, Vol. 10, No. 11, 438, 13.11.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Humanization of the prostate microenvironment reduces homing of PC3 prostate cancer cells to human tissue-engineered bone

AU - McGovern, Jacqui A.

AU - Shafiee, Abbas

AU - Wagner, Ferdinand

AU - Lahr, Christoph A.

AU - Landgraf, Marietta

AU - Meinert, Christoph

AU - Williams, Elizabeth D.

AU - Russell, Pamela J.

AU - Clements, Judith A.

AU - Loessner, Daniela

AU - Holzapfel, Boris M.

AU - Risbridger, Gail P.

AU - Hutmacher, Dietmar W.

PY - 2018/11/13

Y1 - 2018/11/13

N2 - The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice. The hTEBC formed a physiologically mature organ bone which allowed homing of metastatic PCa cells. Humanization of prostate tissue had no significant effect on the tumor burden at the primary site over the 4 weeks following intraprostatic injection, yet reduced the incidence and burden of metastases in the hTEBC. Spontaneous PCa metastases were detected in the lungs and spleen with no significant differences between the humanized and non-humanized prostate groups. A significantly greater metastatic tumor burden was observed in the liver when metastasis occurred from the humanized prostate. Together, our data suggests that the presence of human-derived CAFs and BVECs in the primary PCa microenvironment influences selectively the metastatic and homing behavior of PC3 cells in this model. Our orthotopic and humanized prostate cancer model developed via convergence of cancer research and tissue engineering concepts provides an important platform to study species-specific PCa bone metastasis and to develop and test therapeutic strategies.

AB - The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice. The hTEBC formed a physiologically mature organ bone which allowed homing of metastatic PCa cells. Humanization of prostate tissue had no significant effect on the tumor burden at the primary site over the 4 weeks following intraprostatic injection, yet reduced the incidence and burden of metastases in the hTEBC. Spontaneous PCa metastases were detected in the lungs and spleen with no significant differences between the humanized and non-humanized prostate groups. A significantly greater metastatic tumor burden was observed in the liver when metastasis occurred from the humanized prostate. Together, our data suggests that the presence of human-derived CAFs and BVECs in the primary PCa microenvironment influences selectively the metastatic and homing behavior of PC3 cells in this model. Our orthotopic and humanized prostate cancer model developed via convergence of cancer research and tissue engineering concepts provides an important platform to study species-specific PCa bone metastasis and to develop and test therapeutic strategies.

KW - Bone metastasis

KW - Cancer-associated fibroblast

KW - Humanized bone

KW - Orthotopic model

KW - Prostate cancer

KW - Tissue engineering

KW - Tumor microenvironment

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