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Advantages and limitations of 3D organoids and ex vivo tumor tissue culture in personalized medicine for prostate cancer

类有机物 离体 前列腺癌 体内 病理 癌症 细胞角蛋白 器官培养 基质凝胶 细胞培养 前列腺 组织培养 生物 癌症研究 医学 免疫组织化学 体外 内科学 细胞生物学 生物技术 生物化学 遗传学
作者
Alena Mičková,Martin Morong,Monika Levková,Daniela Kurfürstová,Gvantsa Kharaishvili,Ivo Überall,Vladimír Študent,Stanislav Drápela,Karel Souček,Jan Bouchal
出处
期刊:Klinická onkologie [Care Comm]
卷期号:35 (6) 被引量:3
标识
DOI:10.48095/ccko2022473
摘要

Current in vitro model systems do not fully reflect the bio-logical and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that may better recapitulate disease heterogeneity and retain parental tumor characteristics. Short-term ex vivo culture of PCa tissues may also facilitate drug testing in personalized medicine.For organoid culture, we have processed both cancer and normal tissues from 50 patients who underwent radical prostatectomy or transurethral resection of the prostate. In addition, we exploited the ex vivo tissue culture technique and performed short-term chemotherapy assay using gemcitabine and Chk1 inhibitor MU380 in 10 patient samples.In total, we were able to cultivate organoids from 58% of tumors (29/50) and 69% of normal tissue (20/29). Immunohistochemical staining of two representative cases revealed cell positivity for pan-cytokeratin confirming the presence of epithelial cells. However, the overexpression of AMACR and ERG proteins in tumors was not recapitulated in organoids. Another limitation was the propagation of organoids only up to 3 weeks till the first passage. Next, a short-term drug test was performed for ten patients using ex vivo tissue culture. Samples from prostatectomies mostly presented a low proliferation rate as assessed by Ki-67 staining. Another drawback of this ap-proach was inconsistent tissue morphology among particular tissue fragments. Only one case showed a high proliferation rate for drug testing and tumor tissue was present in all tested samples. In our work, we also provide an overview of recent studies and a detailed comparison of culture conditions.We have established cultures of both organoids and tissue fragments from PCa patient samples. However, the expression of tumor markers was not recapitulated in organoids. Inconsistent morphology among tissue fragments and low proliferation hampered the interpretation of the drug testing in most cases. Still, these approaches may be promising using tissues from metastatic castration-resistant prostate cancer.
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