Granot, D. and Kunz-Schughart, Leoni A. and Neeman, M. (2005) Labeling fibroblasts with biotin-BSA-GdDTPA-FAM for tracking of tumor-associated stroma by fluorescence and MR imaging. MAGNETIC RESONANCE IN MEDICINE, 54 (4). pp. 789-797. ISSN 0740-3194, 1522-2594
Full text not available from this repository. (Request a copy)Abstract
Fibroblasts at the tumor-host interface can differentiate into myofibroblasts and pericytes, and contribute to the guidance and stabilization of endothelial sprouts. After intravenous administration of biotin-BSA-GdDTPA-FAM in mice with subcutaneous MLS human ovarian carcinoma tumors, the distribution of the macromolecular MRI/optical contrast material was confined to blood vessels in normal tissues, while it co-registered with alpha SMA-positive stroma tracks within the tumor. These alpha SMA-positive tumor-associated myofibroblasts and pericytes showed uptake of the contrast material into intracellular granules. We evaluated the use of this contrast material for in vitro labeling of tumor fibroblasts as an approach for tracking their involvement in angiogenesis. Fluorescence microscopy demonstrated internalization of the contrast material, and MRI revealed a significant increase in the R, relaxation rate of labeled fibroblasts. R-1 not only remained elevated for 2 weeks in culture, it also increased with cell proliferation, indicating prolonged retention of the contrast material and subsequent intracellular processing and redistribution of the material, and thereby enhancing MR contrast. Moreover, cells that were labeled ex vivo with MR contrast material and co-inoculated with tumor cells in mice were detected in vivo by MRI. Uptake of the contrast material was suppressed by nystatin, suggesting internalization by caveolae-mediated endocytosis. This study shows that labeling of fibroblasts with biotin-BSA-GdDTPA-FAM is feasible and would allow noninvasive in vivo tracking of fibroblasts during tumor angiogenesis and vessel maturation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAGNETIC-RESONANCE; VASCULAR MATURATION; MALIGNANT BREAST; MAMMALIAN-CELLS; CARCINOMA; CANCER; TISSUE; ANGIOGENESIS; PROGRESSION; CAVEOLIN-1; fibroblasts; fluorescence microscopy; angiogenesis; caveolae; MR contrast |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Apr 2021 12:12 |
| Last Modified: | 26 Apr 2021 12:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35601 |
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