期刊
BRITISH JOURNAL OF CANCER
卷 110, 期 10, 页码 2604-2614出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.160
关键词
tissue culture; ex vivo model; carcinoma in situ; seminoma; pathogenesis of testicular cancer; activin signalling
类别
资金
- Danish Cancer Society
- Familien Erichsens Mindefond and Dagmar Marshalls Fond
- Australian National Health and Medicinal Research Council [APP100248, APP1021156]
- Research Fund at Rigshospitalet grant [9615.06.1.15]
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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