Infiltration of Blood Outgrowth Endothelial Cells into Tumor Spheroids: Role of Matrix Metalloproteinases and Irradiation

• Published in: Anticancer research 2007-05, Vol.27 (3B), p.1415-1421
• Main Authors: Wei, Jiwu, Zhou, Shaoxia, Bachem, Max Georg, Debatin, Klaus-Michael, Beltinger, Christian
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Cells - enzymology; Blood Cells - physiology; Blood Cells - radiation effects; Cell Movement - drug effects; Cell Movement - radiation effects; Edetic Acid - pharmacology; Endothelial Cells - enzymology; Endothelial Cells - physiology; Endothelial Cells - radiation effects; Humans; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 2 - physiology; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase 9 - physiology; Matrix Metalloproteinase Inhibitors; Medical sciences; Mice; Miscellaneous; Paracrine Communication; Radiation; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Spheroids, Cellular - physiology; Tumor Cells, Cultured; Tumors; Up-Regulation
• ISSN: 0250-7005; 1791-7530

Background: Human blood outgrowth endothelial cells (BOECs), used as cellular vehicles for experimental cancer therapy, infiltrate tumors. Infiltration may determine their therapeutic efficacy. The role of matrix metalloproteinases (MMPs) in BOEC infiltration and its potential enhancement by irradiation were investigated. Materials and Methods: Infiltration of BOECs into spheroids made of tumor cells and fibroblasts was determined in the presence of low-dose EDTA, a potent inhibitor of MMPs. Expression and secretion of MMP-2 and -9 by these tumor cells and tumor-stromal cells were investigated with zymography and immunohistochemistry. Results: Infiltration of BOECs into spheroids was blocked by low-dose EDTA. Irradiation enhanced secretion of MMP-2 and, less so, of MMP-9 by tumor-stromal cells and tumor cells, and increased the amount of MMP-2 and -9 in subcutaneous LLC tumors. However, irradiation did not increase infiltration by BOECs. Conclusion: MMPs are involved in the infiltration of BOECs into spheroids. Infiltration of BOECs is not increased by irradiation at the doses employed.