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. 2023 Aug 10;42:203. doi: 10.1186/s13046-023-02785-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 7 — Targeting mutp53-ENTPD5 signaling inhibits ITGA5 expression, tumor growth, and metastasis in a preclinical PDAC model. a PDAC model: parental MIA PaCa-2 and MIA PaCa-2 pIND-ENTPD5 cells (with tet-inducible expression of ENTPD5) were ex vivo labeled with a tandem GLuc-FLuc construct and orthotopically injected into the pancreas of immunodeficient mice. Mice were treated with either Ganetespib (Ganet) or vehicle. All mice received doxycycline. Total tumor growth was measured by blood levels of GLuc. Liver metastasis was quantified by FLuc measurement of liver lysates. Image created with BioRender.com. b-c Total tumor growth in mice transplanted with (b) parental (n = 22 each group) and (c) ENTPD5-overexpressing MIA PaCa-2 tumors (n = 15 each group). Shown is GLuc blood activity in relative light units (RLU) as a surrogate marker of the total tumor burden. d Liver metastasis is shown as FLuc activity (RLU, relative light units) of liver lysates. The number of animals with and without liver metastases in each group is indicated below the graph. e Pancreatic mouse tumors were analyzed by HE staining and immunohistochemistry for (mutant) p53, ENTPD5, and ITGA5. All boxplots show the minimum value, the first quartile, the median, the third quartile, and the maximum value. Single data points represent individual mice. Statistical significance was tested using two-way ANOVA followed by Dunnett’s multiple comparisons test