1. Imaging the interaction of α v integrin-GFP in osteosarcoma cells with RFP-expressing host stromal cells and tumor-scaffold collagen in the primary and metastatic tumor microenvironment.
- Author
-
Tome Y, Kiyuna T, Uehara F, Bouvet M, Tsuchiya H, Kanaya F, and Hoffman RM
- Subjects
- Animals, Bone Neoplasms pathology, Cell Line, Tumor, Fibroblasts metabolism, Green Fluorescent Proteins genetics, Humans, Integrin alphaV genetics, Lung Neoplasms secondary, Macrophages metabolism, Male, Mice, Mice, Nude, Mice, Transgenic, Microscopy, Confocal, Osteosarcoma pathology, Transfection, Transplantation, Heterologous, Red Fluorescent Protein, Bone Neoplasms metabolism, Collagen metabolism, Green Fluorescent Proteins metabolism, Integrin alphaV metabolism, Luminescent Proteins metabolism, Lung Neoplasms metabolism, Osteosarcoma metabolism, Stromal Cells metabolism, Tumor Microenvironment
- Abstract
Human osteosarcoma 143B cells were previously stably transfected with an α
v integrin green flourescent protein (GFP) vector. 143B cells expressing αv integrin-GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP-expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of αv integrin-GFP expression in 143B cells with RFP-expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000. Collagen fibers were imaged simultaneously in reflectance mode. The RFP-expressing stroma included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) which persisted even 3 weeks after passage to nontransgenic nude mice. CAFs expressing RFP were aligned between collagen fibers and cancer cells expressing αv integrin-GFP. Six weeks after transplantation, pulmonary metastases expressing αv integrin-GFP could be identified. TAMs expressing RFP accompanied metastasized osteosarcoma cells expressing αv integrin-GFP in the lung. The current study demonstrates the importance of αv integrin interaction with stromal elements in osteosarcoma., (© 2018 Wiley Periodicals, Inc.)- Published
- 2019
- Full Text
- View/download PDF