{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T13:19:32Z","timestamp":1794057572891,"version":"4.8.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-97983-4","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T09:17:26Z","timestamp":1747041446000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tumor microenvironment modulation by SERPINE1 increases radioimmunotherapy in murine model of gastric cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Javeria","family":"Zaheer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joycie","family":"Shanmugiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyoun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeongi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Su","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"97983_CR1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S2468-1253(19)30328-0","volume":"5","author":"A Etemadi","year":"2020","unstructured":"Etemadi, A. et al. The global, regional, and national burden of stomach cancer in 195 countries, 1990\u20132017: A systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol. Hepatol. 5, 42\u201354. https:\/\/doi.org\/10.1016\/S2468-1253(19)30328-0 (2020).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"97983_CR2","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1517\/14712590903439702","volume":"9","author":"J Meza-Junco","year":"2009","unstructured":"Meza-Junco, J., Au, H. J. & Sawyer, M. B. Trastuzumab for gastric cancer. Expert Opin. Biol. Ther. 9, 1543\u20131551. https:\/\/doi.org\/10.1517\/14712590903439702 (2009).","journal-title":"Expert Opin. Biol. Ther."},{"key":"97983_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194708","author":"J Zaheer","year":"2019","unstructured":"Zaheer, J., Kim, H., Lee, Y. J., Lim, S. M. & Kim, J. S. Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms20194708 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"97983_CR4","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000763","author":"BK Jung","year":"2020","unstructured":"Jung, B. K. et al. Relaxin-expressing oncolytic adenovirus induces remodeling of physical and immunological aspects of cold tumor to potentiate PD-1 blockade. J. Immunother. Cancer https:\/\/doi.org\/10.1136\/jitc-2020-000763 (2020).","journal-title":"J. Immunother. Cancer"},{"key":"97983_CR5","doi-asserted-by":"publisher","first-page":"5579","DOI":"10.3390\/ijms20225579","volume":"20","author":"J Zaheer","year":"2019","unstructured":"Zaheer, J., Kim, H., Lee, Y.-J., Kim, J. S. & Lim, S. M. Combination Radioimmunotherapy Strategies for Solid Tumors. Int. J. Mol. Sci. 20, 5579 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"97983_CR6","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s13139-015-0392-7","volume":"50","author":"JS Kim","year":"2016","unstructured":"Kim, J. S. Combination radioimmunotherapy approaches and quantification of Immuno-PET. Nucl. Med. Mol. Imaging 50, 104\u2013111. https:\/\/doi.org\/10.1007\/s13139-015-0392-7 (2016).","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"97983_CR7","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1038\/ncomms3516","volume":"4","author":"VP Chauhan","year":"2013","unstructured":"Chauhan, V. P. et al. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat. Commun. 4, 2516. https:\/\/doi.org\/10.1038\/ncomms3516 (2013).","journal-title":"Nat. Commun."},{"key":"97983_CR8","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.1073\/pnas.1018892108","volume":"108","author":"B Diop-Frimpong","year":"2011","unstructured":"Diop-Frimpong, B., Chauhan, V. P., Krane, S., Boucher, Y. & Jain, R. K. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proc. Natl. Acad. Sci. U S A 108, 2909\u20132914. https:\/\/doi.org\/10.1073\/pnas.1018892108 (2011).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"97983_CR9","first-page":"2497","volume":"60","author":"PA Netti","year":"2000","unstructured":"Netti, P. A., Berk, D. A., Swartz, M. A., Grodzinsky, A. J. & Jain, R. K. Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res 60, 2497\u20132503 (2000).","journal-title":"Cancer Res"},{"key":"97983_CR10","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1073\/pnas.1818357116","volume":"116","author":"Y Zhao","year":"2019","unstructured":"Zhao, Y. et al. Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma. Proc. Natl. Acad. Sci. 116, 2210\u20132219. https:\/\/doi.org\/10.1073\/pnas.1818357116 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"97983_CR11","doi-asserted-by":"publisher","first-page":"753330","DOI":"10.3389\/fonc.2021.753330","volume":"11","author":"Z Yang","year":"2021","unstructured":"Yang, Z. et al. Extracellular matrix characterization in gastric cancer helps to predict prognosis and chemotherapy response. Front. Oncol. 11, 753330. https:\/\/doi.org\/10.3389\/fonc.2021.753330 (2021).","journal-title":"Front. Oncol."},{"key":"97983_CR12","doi-asserted-by":"publisher","first-page":"4768","DOI":"10.1158\/0008-5472.Can-03-1472","volume":"64","author":"L Eikenes","year":"2004","unstructured":"Eikenes, L., Bruland, \u00d8. S., Brekken, C. & Davies, C. D. L. Collagenase increases the transcapillary pressure gradient and improves the uptake and distribution of monoclonal antibodies in human osteosarcoma xenografts. Cancer Res. 64, 4768\u20134773. https:\/\/doi.org\/10.1158\/0008-5472.Can-03-1472 (2004).","journal-title":"Cancer Res."},{"key":"97983_CR13","first-page":"3513","volume":"20","author":"C Brekken","year":"2000","unstructured":"Brekken, C., Hjelstuen, M. H., Bruland, \u00d8. S. & de Lange, D. C. Hyaluronidase-induced periodic modulation of the interstitial fluid pressure increases selective antibody uptake in human osteosarcoma xenografts. Anticancer Res. 20, 3513\u20133519 (2000).","journal-title":"Anticancer Res."},{"key":"97983_CR14","doi-asserted-by":"publisher","first-page":"10664","DOI":"10.1158\/0008-5472.Can-07-3107","volume":"67","author":"W Mok","year":"2007","unstructured":"Mok, W., Boucher, Y. & Jain, R. K. Matrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus. Cancer Res. 67, 10664\u201310668. https:\/\/doi.org\/10.1158\/0008-5472.Can-07-3107 (2007).","journal-title":"Cancer Res."},{"key":"97983_CR15","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nrc3925","volume":"15","author":"SM Larson","year":"2015","unstructured":"Larson, S. M., Carrasquillo, J. A., Cheung, N. K. & Press, O. W. Radioimmunotherapy of human tumours. Nat. Rev. Cancer 15, 347\u2013360. https:\/\/doi.org\/10.1038\/nrc3925 (2015).","journal-title":"Nat. Rev. Cancer"},{"key":"97983_CR16","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1080\/1120009X.2019.1687996","volume":"31","author":"J-D Yang","year":"2019","unstructured":"Yang, J.-D., Ma, L. & Zhu, Z. SERPINE1 as a cancer-promoting gene in gastric adenocarcinoma: facilitates tumour cell proliferation, migration, and invasion by regulating EMT. J. Chemother. 31, 408\u2013418. https:\/\/doi.org\/10.1080\/1120009X.2019.1687996 (2019).","journal-title":"J. Chemother."},{"key":"97983_CR17","doi-asserted-by":"publisher","first-page":"e7091","DOI":"10.7717\/peerj.7091","volume":"7","author":"B Xu","year":"2019","unstructured":"Xu, B., Bai, Z., Yin, J. & Zhang, Z. Global transcriptomic analysis identifies SERPINE1 as a prognostic biomarker associated with epithelial-to-mesenchymal transition in gastric cancer. PeerJ 7, e7091. https:\/\/doi.org\/10.7717\/peerj.7091 (2019).","journal-title":"PeerJ"},{"key":"97983_CR18","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3109\/14756366.2016.1161620","volume":"31","author":"A Jab\u0142o\u0144ska-Trypu\u0107","year":"2016","unstructured":"Jab\u0142o\u0144ska-Trypu\u0107, A., Matejczyk, M. & Rosochacki, S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J. Enzyme Inhibition Med. Chem. 31, 177\u2013183. https:\/\/doi.org\/10.3109\/14756366.2016.1161620 (2016).","journal-title":"J. Enzyme Inhibition Med. Chem."},{"key":"97983_CR19","doi-asserted-by":"publisher","first-page":"5872","DOI":"10.1074\/jbc.270.11.5872","volume":"270","author":"RT Aimes","year":"1995","unstructured":"Aimes, R. T. & Quigley, J. P. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3\/4- and 1\/4-length fragments. J. Biol. Chem. 270, 5872\u20135876. https:\/\/doi.org\/10.1074\/jbc.270.11.5872 (1995).","journal-title":"J. Biol. Chem."},{"key":"97983_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41419-021-04493-y","volume":"13","author":"Y Huang","year":"2022","unstructured":"Huang, Y. et al. RNF12 is regulated by AKT phosphorylation and promotes TGF-\u03b2 driven breast cancer metastasis. Cell Death Dis. 13, 44. https:\/\/doi.org\/10.1038\/s41419-021-04493-y (2022).","journal-title":"Cell Death Dis."},{"key":"97983_CR21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41389-021-00302-5","volume":"10","author":"H Yoon","year":"2021","unstructured":"Yoon, H. et al. TGF-\u03b21-mediated transition of resident fibroblasts to cancer-associated fibroblasts promotes cancer metastasis in gastrointestinal stromal tumor. Oncogenesis 10, 13. https:\/\/doi.org\/10.1038\/s41389-021-00302-5 (2021).","journal-title":"Oncogenesis"},{"key":"97983_CR22","doi-asserted-by":"publisher","first-page":"e36258","DOI":"10.1371\/journal.pone.0036258","volume":"7","author":"M Heine","year":"2012","unstructured":"Heine, M. et al. High Interstitial fluid pressure is associated with low Tumour Penetration of Diagnostic Monoclonal Antibodies applied for molecular imaging purposes. PLoS ONE 7, e36258. https:\/\/doi.org\/10.1371\/journal.pone.0036258 (2012).","journal-title":"PLoS ONE"},{"key":"97983_CR23","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s13139-019-00598-7","volume":"53","author":"HG Kim","year":"2019","unstructured":"Kim, H. G. et al. Measurement of tumor pressure and strategies of imaging tumor pressure for radioimmunotherapy. Nucl. Med. Mol. Imaging 53, 235\u2013241. https:\/\/doi.org\/10.1007\/s13139-019-00598-7 (2019).","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"97983_CR24","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/nrc1456","volume":"4","author":"CH Heldin","year":"2004","unstructured":"Heldin, C. H., Rubin, K., Pietras, K. & Ostman, A. High interstitial fluid pressure - an obstacle in cancer therapy. Nat. Rev. Cancer 4, 806\u2013813. https:\/\/doi.org\/10.1038\/nrc1456 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"97983_CR25","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2967\/jnumed.107.046888","volume":"49","author":"A Khaibullina","year":"2008","unstructured":"Khaibullina, A. et al. Pulsed High-Intensity Focused Ultrasound Enhances Uptake of Radiolabeled Monoclonal Antibody to Human Epidermoid Tumor in Nude Mice. J. Nucl. Med. 49, 295\u2013302. https:\/\/doi.org\/10.2967\/jnumed.107.046888 (2008).","journal-title":"J. Nucl. Med."},{"key":"97983_CR26","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.nucmedbio.2011.10.020","volume":"39","author":"BS Jang","year":"2012","unstructured":"Jang, B. S. et al. Combined-modality radioimmunotherapy: synergistic effect of paclitaxel and additive effect of bevacizumab. Nucl. Med. Biol. 39, 472\u2013483. https:\/\/doi.org\/10.1016\/j.nucmedbio.2011.10.020 (2012).","journal-title":"Nucl. Med. Biol."},{"key":"97983_CR27","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jconrel.2012.06.025","volume":"162","author":"S Wang","year":"2012","unstructured":"Wang, S. et al. Pulsed high intensity focused ultrasound increases penetration and therapeutic efficacy of monoclonal antibodies in murine xenograft tumors. J Control Release 162, 218\u2013224. https:\/\/doi.org\/10.1016\/j.jconrel.2012.06.025 (2012).","journal-title":"J Control Release"},{"key":"97983_CR28","doi-asserted-by":"publisher","first-page":"041011","DOI":"10.1115\/1.2939310","volume":"130","author":"Y Lu","year":"2008","unstructured":"Lu, Y. & Wang, W. Interaction between the interstitial fluid and the extracellular matrix in confined indentation. J. Biomech. Eng. 130, 041011. https:\/\/doi.org\/10.1115\/1.2939310 (2008).","journal-title":"J. Biomech. Eng."},{"key":"97983_CR29","first-page":"5110","volume":"52","author":"Y Boucher","year":"1992","unstructured":"Boucher, Y. & Jain, R. K. Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. Cancer Res 52, 5110\u20135114 (1992).","journal-title":"Cancer Res"},{"key":"97983_CR30","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1096\/fj.02-1201fje","volume":"17","author":"AV Salnikov","year":"2003","unstructured":"Salnikov, A. V. et al. Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy. Faseb j. 17, 1756\u20131758. https:\/\/doi.org\/10.1096\/fj.02-1201fje (2003).","journal-title":"Faseb j."},{"key":"97983_CR31","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1093\/cvr\/cvq143","volume":"87","author":"RK Reed","year":"2010","unstructured":"Reed, R. K. & Rubin, K. Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix. Cardiovas. Res. 87, 211\u2013217. https:\/\/doi.org\/10.1093\/cvr\/cvq143 (2010).","journal-title":"Cardiovas. Res."},{"key":"97983_CR32","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1160\/th16-04-0306","volume":"116","author":"X Zhou","year":"2016","unstructured":"Zhou, X., Hendrickx, M. L., Hassanzadeh-Ghassabeh, G., Muyldermans, S. & Declerck, P. J. Generation and in vitro characterisation of inhibitory nanobodies towards plasminogen activator inhibitor 1. Thromb. Haemost 116, 1032\u20131040. https:\/\/doi.org\/10.1160\/th16-04-0306 (2016).","journal-title":"Thromb. Haemost"},{"key":"97983_CR33","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1364\/OL.44.003928","volume":"44","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y. et al. Automatic segmentation of intravital fluorescence microscopy images by K-means clustering of FLIM phasors. Opt. Lett. 44, 3928\u20133931. https:\/\/doi.org\/10.1364\/OL.44.003928 (2019).","journal-title":"Opt. Lett."},{"key":"97983_CR34","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1002\/cphc.200800693","volume":"10","author":"J Irrgang","year":"2009","unstructured":"Irrgang, J., Ksienczyk, J., Lapiene, V. & Niemeyer, C. M. Analysis of Non-Covalent Bioconjugation of Colloidal Nanoparticles by Means of Atomic Force Microscopy and Data Clustering. Chem. Phys. Chem. 10, 1483\u20131491. https:\/\/doi.org\/10.1002\/cphc.200800693 (2009).","journal-title":"Chem. Phys. Chem."},{"key":"97983_CR35","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","volume":"347","author":"M Uhl\u00e9n","year":"2015","unstructured":"Uhl\u00e9n, M. et al. Tissue-based map of the human proteome. Science 347, 1260419. https:\/\/doi.org\/10.1126\/science.1260419 (2015).","journal-title":"Science"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-97983-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-97983-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-97983-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T09:17:27Z","timestamp":1747041447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-97983-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["97983"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-97983-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"6 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest. The funders had no role in the study design, collection, analysis, interpretation of data, writing of the manuscript, or in the decision to publish the results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Ethical approval and consent to participate: All experiments were performed under a protocol approved by the IACUC (approval number: KIRAMS 2020\u20130027) of the Korea Institute of Radiological and Medical Sciences (KIRAMS). The study is reported in accordance with ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"16449"}}