Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas
Summary: The patient-derived xenograft (PDX) model is a versatile tool used to study the tumor microenvironment (TME). However, limited studies have described multi-tumor PDX screening strategies to detect hub regulators during cancer-stroma interaction. Transcriptomes of cancer (human) and stroma (...
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oai:doaj.org-article:49010a93e08142cb8533d7ed48938bcf2021-11-20T05:09:55ZMulti-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas2589-004210.1016/j.isci.2021.103322https://doaj.org/article/49010a93e08142cb8533d7ed48938bcf2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012918https://doaj.org/toc/2589-0042Summary: The patient-derived xenograft (PDX) model is a versatile tool used to study the tumor microenvironment (TME). However, limited studies have described multi-tumor PDX screening strategies to detect hub regulators during cancer-stroma interaction. Transcriptomes of cancer (human) and stroma (mouse) components of 70 PDX samples comprising 9 distinctive tumor types were analyzed in this study. PDX models recapitulated the original tumors' features, including tumor composition and putative signaling. Particularly, kidney renal clear cell carcinoma (KIRC) stood out, with altered hypoxia-related pathways and a high proportion of endothelial cells in the TME. Furthermore, an integrated analysis conducted to predict paracrine effectors in the KIRC cancer-to-stroma communication detected well-established soluble factors responsible for the hypoxia-related reaction and the so-far unestablished soluble factor, apelin (APLN). Subsequent experiments also supported the potential role of APLN in KIRC tumor progression. Therefore, this paper hereby provides an analytical workflow to find hub regulators in cancer-stroma interactions.Kuniyo SueyoshiDaisuke KomuraHiroto KatohAsami YamamotoTakumi OnoyamaTsuyoshi ChijiwaTakayuki IsagawaMariko TanakaHiroshi SuemizuMasato NakamuraYohei MiyagiHiroyuki AburataniShumpei IshikawaElsevierarticleCancer systems biologyCancerScienceQENiScience, Vol 24, Iss 11, Pp 103322- (2021) |
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Cancer systems biology Cancer Science Q |
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Cancer systems biology Cancer Science Q Kuniyo Sueyoshi Daisuke Komura Hiroto Katoh Asami Yamamoto Takumi Onoyama Tsuyoshi Chijiwa Takayuki Isagawa Mariko Tanaka Hiroshi Suemizu Masato Nakamura Yohei Miyagi Hiroyuki Aburatani Shumpei Ishikawa Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
description |
Summary: The patient-derived xenograft (PDX) model is a versatile tool used to study the tumor microenvironment (TME). However, limited studies have described multi-tumor PDX screening strategies to detect hub regulators during cancer-stroma interaction. Transcriptomes of cancer (human) and stroma (mouse) components of 70 PDX samples comprising 9 distinctive tumor types were analyzed in this study. PDX models recapitulated the original tumors' features, including tumor composition and putative signaling. Particularly, kidney renal clear cell carcinoma (KIRC) stood out, with altered hypoxia-related pathways and a high proportion of endothelial cells in the TME. Furthermore, an integrated analysis conducted to predict paracrine effectors in the KIRC cancer-to-stroma communication detected well-established soluble factors responsible for the hypoxia-related reaction and the so-far unestablished soluble factor, apelin (APLN). Subsequent experiments also supported the potential role of APLN in KIRC tumor progression. Therefore, this paper hereby provides an analytical workflow to find hub regulators in cancer-stroma interactions. |
format |
article |
author |
Kuniyo Sueyoshi Daisuke Komura Hiroto Katoh Asami Yamamoto Takumi Onoyama Tsuyoshi Chijiwa Takayuki Isagawa Mariko Tanaka Hiroshi Suemizu Masato Nakamura Yohei Miyagi Hiroyuki Aburatani Shumpei Ishikawa |
author_facet |
Kuniyo Sueyoshi Daisuke Komura Hiroto Katoh Asami Yamamoto Takumi Onoyama Tsuyoshi Chijiwa Takayuki Isagawa Mariko Tanaka Hiroshi Suemizu Masato Nakamura Yohei Miyagi Hiroyuki Aburatani Shumpei Ishikawa |
author_sort |
Kuniyo Sueyoshi |
title |
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
title_short |
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
title_full |
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
title_fullStr |
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
title_full_unstemmed |
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
title_sort |
multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas |
publisher |
Elsevier |
publishDate |
2021 |
url |
https://doaj.org/article/49010a93e08142cb8533d7ed48938bcf |
work_keys_str_mv |
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