Am J Cancer Res 2012;2(5):581-588
Original Article
Vascular development in mouse lung metastases
Howard W Salmon, Ananya Guha, Amyn M Rojiani, Dietmar W Siemann
Radiation Physics, North Florida Regional Medical Center, Gainesville, FL, USA; College of Medicine, University of Florida,
Gainesville, Florida, USA; Department of Pathology, Medical College of Georgia, Augusta, Georgia, USA; 4Department of
Radiation Oncology, College of Medicine, University of Florida ,Shands Cancer Center, Gainesville, Florida, USA
Received July 23, 2012; accepted August 10, 2012; Epub August 20, 2012; Published September 15, 2012
Abstract: Dissemination of cancer cells is strongly associated with reduction in quality of life, worsening of prognosis, and
remains the primary cause of therapeutic failure and high mortality in cancer. A crucial factor in the progression of metastases is
the ability to establish a functioning blood vessel network. Consequently therapeutic strategies which selectively target tumor
vasculature may hold promise for the treatment of metastatic disease. A complicating factor in the assessment of the efficacy of
vascular targeting therapies is that the metastatic process can result in multiple neoplastic lesions at various stages of growth
and vascularity in a single organ. The goal of this project was to utilize a rodent squamous cell carcinoma (SCCVII) model to
characterize the development of metastatic lung lesions and their associated vasculature. Mice were injected with tumor cells via
the tail vein to introduce a reproducible number of lung metastases. At various times after cell injection, lungs were removed and
serial sections were taken throughout the lobes for morphometric analysis. Tumor volumes were calculated for each nodule
using 2 hematoxylin and eosin (H&E) stained sections that were a known distance apart. Sections adjacent to those used for
size determination were reserved for immunohistochemical staining with CD31 to identify blood vessels associated with each
nodule. The results showed that although the median tumor volume increased from 0.006 to 0.51 mm3 between 7 and 18 days
post SCCVII cell injection, a range of tumor sizes existed at all-times. Irrespective of the time of assessment, nodules with
volumes < 0.5 mm3 had a constant vessel density while those with volumes >0.5 mm3 showed increasing vessel densities with
increasing size. These findings indicate that the methodology outlined in this study can identify metastases in various stages of
vascular development and could therefore be applied to evaluate and distinguish therapeutic interventions that seek to prevent
the initiation of blood vessel networks and those targeting already established expanding tumor vasculature. Examining the
efficacy of such approaches, alone or in combination, in the treatment of metastases in a preclinical model could lead to the
development of more effective therapeutic strategies for metastatic disease. (AJCR0000138).
Keywords: Metastasis, vascular development, carcinoma
Address all correspondence to:
Dr. Dietmar W. Siemann
Department of Radiation Oncology
University of Florida
2000 SW Archer Road
Gainesville, FL 32610, USA.
E-mail: siemadw@ufl.edu
Original Article
Vascular development in mouse lung metastases
Howard W Salmon, Ananya Guha, Amyn M Rojiani, Dietmar W Siemann
Radiation Physics, North Florida Regional Medical Center, Gainesville, FL, USA; College of Medicine, University of Florida,
Gainesville, Florida, USA; Department of Pathology, Medical College of Georgia, Augusta, Georgia, USA; 4Department of
Radiation Oncology, College of Medicine, University of Florida ,Shands Cancer Center, Gainesville, Florida, USA
Received July 23, 2012; accepted August 10, 2012; Epub August 20, 2012; Published September 15, 2012
Abstract: Dissemination of cancer cells is strongly associated with reduction in quality of life, worsening of prognosis, and
remains the primary cause of therapeutic failure and high mortality in cancer. A crucial factor in the progression of metastases is
the ability to establish a functioning blood vessel network. Consequently therapeutic strategies which selectively target tumor
vasculature may hold promise for the treatment of metastatic disease. A complicating factor in the assessment of the efficacy of
vascular targeting therapies is that the metastatic process can result in multiple neoplastic lesions at various stages of growth
and vascularity in a single organ. The goal of this project was to utilize a rodent squamous cell carcinoma (SCCVII) model to
characterize the development of metastatic lung lesions and their associated vasculature. Mice were injected with tumor cells via
the tail vein to introduce a reproducible number of lung metastases. At various times after cell injection, lungs were removed and
serial sections were taken throughout the lobes for morphometric analysis. Tumor volumes were calculated for each nodule
using 2 hematoxylin and eosin (H&E) stained sections that were a known distance apart. Sections adjacent to those used for
size determination were reserved for immunohistochemical staining with CD31 to identify blood vessels associated with each
nodule. The results showed that although the median tumor volume increased from 0.006 to 0.51 mm3 between 7 and 18 days
post SCCVII cell injection, a range of tumor sizes existed at all-times. Irrespective of the time of assessment, nodules with
volumes < 0.5 mm3 had a constant vessel density while those with volumes >0.5 mm3 showed increasing vessel densities with
increasing size. These findings indicate that the methodology outlined in this study can identify metastases in various stages of
vascular development and could therefore be applied to evaluate and distinguish therapeutic interventions that seek to prevent
the initiation of blood vessel networks and those targeting already established expanding tumor vasculature. Examining the
efficacy of such approaches, alone or in combination, in the treatment of metastases in a preclinical model could lead to the
development of more effective therapeutic strategies for metastatic disease. (AJCR0000138).
Keywords: Metastasis, vascular development, carcinoma
Address all correspondence to:
Dr. Dietmar W. Siemann
Department of Radiation Oncology
University of Florida
2000 SW Archer Road
Gainesville, FL 32610, USA.
E-mail: siemadw@ufl.edu
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