Infiltration of blood outgrowth endothelial cells into tumor spheroids: role of matrix metalloproteinases and irradiation.
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.


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.


CONCLUSIONS
MMPs are involved in the infiltration of BOECs into spheroids. Infiltration of BOECs is not increased by irradiation at the doses employed.
Wei
Jiwu
J
University Children's Hospital, 89075 Ulm, Germany.
Zhou
Shaoxia
S
Bachem
Max Georg
MG
Debatin
Klaus-Michael
KM
Beltinger
Christian
C
D000818:Animals; D001773:Blood Cells / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D004492:Edetic Acid / Q000494:pharmacology; D042783:Endothelial Cells / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D019899:Paracrine Communication; D011827:Radiation; D018874:Spheroids, Cellular / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D061965:Matrix Metalloproteinase Inhibitors; D004492:Edetic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9