Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche

Anne Jorgensen, Julia Caitlin Young, John Nielsen, Ulla Nordstrom Joensen, Birgitte Gronkaer Toft, Ewa Rajpert-De Meyts, Katherine A L Loveland

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

BACKGROUND: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were cultured in hanging drops and effects of activin A and follistatin treatment were investigated in seminoma cultures. RESULTS: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. CONCLUSIONS: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.
Original languageEnglish
Pages (from-to)2604 - 2614
Number of pages11
JournalBritish Journal of Cancer
Volume110
Issue number10
DOIs
Publication statusPublished - 2014

Cite this

Jorgensen, Anne ; Young, Julia Caitlin ; Nielsen, John ; Joensen, Ulla Nordstrom ; Toft, Birgitte Gronkaer ; Rajpert-De Meyts, Ewa ; Loveland, Katherine A L. / Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche. In: British Journal of Cancer. 2014 ; Vol. 110, No. 10. pp. 2604 - 2614.
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title = "Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche",
abstract = "BACKGROUND: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were cultured in hanging drops and effects of activin A and follistatin treatment were investigated in seminoma cultures. RESULTS: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. CONCLUSIONS: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.",
author = "Anne Jorgensen and Young, {Julia Caitlin} and John Nielsen and Joensen, {Ulla Nordstrom} and Toft, {Birgitte Gronkaer} and {Rajpert-De Meyts}, Ewa and Loveland, {Katherine A L}",
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Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche. / Jorgensen, Anne; Young, Julia Caitlin; Nielsen, John; Joensen, Ulla Nordstrom; Toft, Birgitte Gronkaer; Rajpert-De Meyts, Ewa; Loveland, Katherine A L.

In: British Journal of Cancer, Vol. 110, No. 10, 2014, p. 2604 - 2614.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Jorgensen, Anne

AU - Young, Julia Caitlin

AU - Nielsen, John

AU - Joensen, Ulla Nordstrom

AU - Toft, Birgitte Gronkaer

AU - Rajpert-De Meyts, Ewa

AU - Loveland, Katherine A L

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were cultured in hanging drops and effects of activin A and follistatin treatment were investigated in seminoma cultures. RESULTS: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. CONCLUSIONS: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

AB - BACKGROUND: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were cultured in hanging drops and effects of activin A and follistatin treatment were investigated in seminoma cultures. RESULTS: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. CONCLUSIONS: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

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