Organotypic slice cultures of pancreatic ductal adenocarcinoma preserve the tumor microenvironment and provide a platform for drug response |
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Authors: | Chae Yoon Lim Jae Hyuck Chang Won Sun Lee Kang Min Lee Young Chul Yoon Jeana Kim Il Young Park |
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Affiliation: | 1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2. Institute of Clinical Medicine Research, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea;3. Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;4. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea |
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Abstract: | Background/Objective: The conventional models currently used to evaluate various anti-tumor therapeutic agents are not sufficient for representing human pancreatic ductal adenocarcinoma (PDA), which has a unique tumor microenvironment. We aimed to produce an organotypic slice culture model from human PDA that resembles the in vivo situation and to evaluate the responses of PDA slices to established cytotoxic drugs.MethodsPDA tissues were obtained from 10 patients who underwent pancreatic resection. The tissues were sliced by a vibratome, and the tumor slices were then cultured. The viability of tumor slices during slice culture was evaluated using H&E and immunohistochemical staining, and stromal cells were demonstrated. The effects of cytotoxic drugs on PDA cell lines and slices were analyzed.ResultsTumor slices maintained their surface areas and tissue viability for at least five days during culture. Preserved proliferation and apoptosis in tumor slices were observed by the expression of Ki-67 and cleaved caspase-3. Stromal cells including macrophages (CD68+ and CD163+), T cells (CD3+, CD8+, and FOXP3+), and myeloid cells (CD11b+) were present throughout the culture period. Staurosporine, gemcitabine, and cisplatin treatment of PDA cell lines and tumor slices exerted proportional cytotoxic effects in terms of MTT viability, tumor cell number, and Ki-67 and cleaved caspase-3 expression.ConclusionsOrganotypic human PDA slice cultures preserved their viability and tumor microenvironment for at least five days during slice culture. PDA slice culture appears to be a feasible preclinical test model to assess the response to anti-tumor agents. |
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Keywords: | Chemotherapy Immune cells Microenvironment Pancreatic cancer Slice culture |
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