The Natural Progression of Microvasculature in Primary Tumor and Lymph Node Metastases in a Breast Carcinoma Model: Relationship between Microvessel Density, Vascular Endothelial Growth Factor Expression and Metastatic Invasion

The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (I...

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Published in:Cancer biology & therapy 2004-04, Vol.3 (4), p.408-414
Main Authors: Rowe, R. Wanda, Tomoda, Masaaki, Strebel, Frederick R., Jenkins, Gaye N., Stephens, L. Clifton, Bull, Joan M.C.
Format: Article
Language:English
Subjects:
Animals
Binding
Biology
Bioscience
Calcium
Cancer
Carcinoma - blood supply
Carcinoma - pathology
Cell
Cycle
Female
Immunoassay
Landes
Lymphatic Metastasis - physiopathology
Mammary Neoplasms, Animal - blood supply
Mammary Neoplasms, Animal - pathology
Microcirculation
Neoplasm Invasiveness
Neovascularization, Pathologic
Organogenesis
Proteins
Rats
Rats, Inbred F344
Vascular Endothelial Growth Factor A - biosynthesis
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Summary:The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5-6 tumor doublings. Excised tumors were examined for (i) MVD assessed by immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with increasing tumor weight in both primary and metastatic tumors. The MVD saturation level was significantly greater for primary tumors (MVD=22) than for ALNs or ILNs (MVD=14). Maximal VEGF score was not statistically different between the three kinds of tumors, however the rate of rise in VEGF expression was different. Near-maximal VEGF expression occurred early in tumor growth, preceding microvessel development. Both MVD and VEGF expression in lymph nodes were proportional to the pathology score characterizing increasing metastatic invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an ability to survive without significant vasculature. These findings underscore the differences in angiogenesis between primary tumors and LNMs and have implications for therapy of metastatic cancer.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.3.4.779