{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:22Z","timestamp":1772168962856,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.2-129.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions\n                    <ns4:italic>in vivo<\/ns4:italic>\n                    is critical but challenging. Intravital microscopy (IVM) of subcutaneous tumors provides dynamic, continuous, long-term imaging at high resolution. Although popular, subcutaneous tumor models are often criticized for being ectopic and lacking orthotopic tissue microenvironments critical for proper development. Similar IVM of orthotopic and especially spontaneous tumors is seldom possible. Here, we generate and characterize tumor models in mice for breast, lung, prostate and ovarian cancer by co-engrafting tumor spheroids with orthotopic tissue in dorsal skin window chambers for IVM. We use tumor cells and tissue, both genetically engineered to express distinct fluorescent proteins, in order to distinguish neoplastic cells from engrafted tissue. IVM of this new, two-colored model reveals classic tumor morphology with red tumor cell nests surrounded by green stromal elements. The co-implanted tissue forms the supportive stroma and vasculature of these tumors. Tumor growth and angiogenesis are more robust when tumor cells are co-implanted with orthotopic tissue versus other tissues, or in the skin alone. The orthotopic tissue promotes tumor cell mitosis over apoptosis. With time, tumor cells can adapt to new environments and ultimately even grow better in the non-orthotopic tissue over the original orthotopic tissue. These models offer a significant advance by recreating an orthotopic microenvironment in an ectopic location that is still easy to image by IVM. These \u201cectopic-orthotopic\u201d models provide an exceptional way to study tumor and stroma cells in cancer, and directly show the critical importance of microenvironment in the development of multiple tumors.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.2-129.v2","type":"journal-article","created":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T11:14:59Z","timestamp":1377774899000},"page":"129","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors"],"prefix":"10.12688","volume":"2","author":[{"given":"Per","family":"Borgstrom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phil","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Czarny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Racine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan E","family":"Schnitzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2013,8,29]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"8643-53","DOI":"10.1158\/0008-5472.CAN-07-6611","article-title":"A history of cancer chemotherapy.","volume":"68","author":"V DeVita","year":"2008","journal-title":"Cancer Res."},{"key":"ref-2","doi-asserted-by":"crossref","first-page":"971-81","DOI":"10.1158\/1078-0432.971.11.3","article-title":"50 years of preclinical anticancer drug screening: empirical to target-driven approaches.","volume":"11","author":"M Suggitt","year":"2005","journal-title":"Clin Cancer Res."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"579-91","DOI":"10.1038\/nrc2403","article-title":"VEGF-targeted therapy: mechanisms of anti-tumour activity.","volume":"8","author":"L Ellis","year":"2008","journal-title":"Nat Rev Cancer."},{"key":"ref-4","doi-asserted-by":"crossref","first-page":"S134-9","DOI":"10.4161\/cbt.213","article-title":"Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved.","volume":"2","author":"R Kerbel","year":"2003","journal-title":"Cancer Biol Ther."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"266-76","DOI":"10.1038\/nrc778","article-title":"Dissecting tumour pathophysiology using intravital microscopy.","volume":"2","author":"R Jain","year":"2002","journal-title":"Nat Rev Cancer."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"135-52","DOI":"10.1016\/j.addr.2004.07.015","article-title":"Intravital imaging of tumour vascular networks using multi-photon fluorescence microscopy.","volume":"57","author":"G Tozer","year":"2005","journal-title":"Adv Drug Deliv Rev."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"53-61","DOI":"10.1038\/sj.neo.7900062","article-title":"Intravital fluorescence videomicroscopy to study tumor angiogenesis and microcirculation.","volume":"2","author":"P Vajkoczy","year":"2000","journal-title":"Neoplasia (New York, N.Y.)."},{"key":"ref-8","first-page":"753-65","article-title":"Clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: rationale for a three-stage strategy.","volume":"67","author":"M Staquet","year":"1983","journal-title":"Cancer Treat Rep."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"125-34","DOI":"10.1007\/BF01851841","article-title":"Technical report--a new chamber technique for microvascular studies in unanesthetized hamsters.","volume":"177","author":"B Endrich","year":"1980","journal-title":"Res Exp Med (Berl)."},{"key":"ref-10","first-page":"1898-904","article-title":"Quantitative analysis of microvascular structure and function in the amelanotic melanoma A-Mel-3.","volume":"41","author":"K Asaishi","year":"1981","journal-title":"Cancer Res."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"511-9","DOI":"10.1158\/0008-5472.CAN-06-1478","article-title":"Stromal-epithelial cell interactions and androgen receptor-coregulator recruitment is altered in the tissue microenvironment of prostate cancer.","volume":"67","author":"P Cano","year":"2007","journal-title":"Cancer Res."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"224-9","DOI":"10.1186\/bcr300","article-title":"Tumour-stromal interactions. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.2100.r3985, Hong Zhao, Department of Systems Medicine and Bioengineering, Methodist Hospital Research Institute, Houston, TX, USA, 05 Mar 2014, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-129\/v2#referee-response-3985","order":0,"name":"referee-response-3985","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.2100.r3322, Erik Sahai, Tumour Cell Biology Laboratory, Cancer Research UK, London, UK, 23 Jan 2014, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-129\/v2#referee-response-3322","order":1,"name":"referee-response-3322","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was supported by grant funds (to J.E.S.) from the Komen Foundation (KG100983), the Tobacco-Related Disease Research Program (grant 18XT0196 and 20XT0161) the California Breast Cancer Research Program (grant 16IB-0104 and DOD CDMRP W81XWH-11-1-0693) and the National Institute of Health (R01CA115215, P01CA104898, R01CA119378, and R01CA83989).","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original data is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}