Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc]
Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo 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 o...
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doaj-e439dd3cda744c098802cde3f7ce694f2020-11-25T03:31:10ZengF1000 Research LtdF1000Research2046-14022013-08-01210.12688/f1000research.2-129.v22100Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc]Per Borgstrom0Phil Oh1Malgorzata Czarny2Brian Racine3Jan E Schnitzer4Sidney Kimmel Cancer Center, 10905 Road to the Cure, San Diego, CA, 92121, USAProteogenomics Research Institute for Systems Medicine, 11107 Roselle St, San Diego, CA, 92121, USAProteogenomics Research Institute for Systems Medicine, 11107 Roselle St, San Diego, CA, 92121, USASidney Kimmel Cancer Center, 10905 Road to the Cure, San Diego, CA, 92121, USAProteogenomics Research Institute for Systems Medicine, 11107 Roselle St, San Diego, CA, 92121, USATumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo 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 “ectopic-orthotopic” 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.http://f1000research.com/articles/2-129/v2Breast Diseases: Benign & MalignantGenitourinary CancersGynecological CancersLung Cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Per Borgstrom Phil Oh Malgorzata Czarny Brian Racine Jan E Schnitzer |
spellingShingle |
Per Borgstrom Phil Oh Malgorzata Czarny Brian Racine Jan E Schnitzer Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] F1000Research Breast Diseases: Benign & Malignant Genitourinary Cancers Gynecological Cancers Lung Cancer |
author_facet |
Per Borgstrom Phil Oh Malgorzata Czarny Brian Racine Jan E Schnitzer |
author_sort |
Per Borgstrom |
title |
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
title_short |
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
title_full |
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
title_fullStr |
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
title_full_unstemmed |
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
title_sort |
co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors [v2; ref status: indexed, http://f1000r.es/1mc] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2013-08-01 |
description |
Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo 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 “ectopic-orthotopic” 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. |
topic |
Breast Diseases: Benign & Malignant Genitourinary Cancers Gynecological Cancers Lung Cancer |
url |
http://f1000research.com/articles/2-129/v2 |
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