X-rays modulate extracellular matrix in vivo

X-rays have an antiangiogenic effect in the chicken embryo chorioallantoic membrane (CAM) model of in vivo angiogenesis. Our study demonstrates that X -rays induce an early apoptosis of CAM cells, modulate the synthesis and de position of extracellular matrix (ECM) proteins involved in regulating angi ogenesis and affect angiogenesis induced by tumour cells implanted onto the CAM. Apoptosis was evident within 1-2 hr, but not later than 6 hr after ir radiation. Fibronectin, laminin, collagen type I, integrin alpha (v)beta (3 ) and MMP-2 protein amounts were all decreased 6 hr after irradiation. In c ontrast, collagen type IV, which is restricted to basement membrane, was no t affected by irradiation of the CAM. There was a similar decrease of gene expression for fibronectin, laminin, collagen type I and MMP-2, 6 hr after irradiation. The levels of mRNA for integrin alpha (v)beta (3) and collagen type IV were unaffected up to 24 hr after irradiation. The decrease in bot h protein and mRNA levels was reversed at later time points and 48 hr after irradiation, there was a significant increase in the expression of all the genes studied. When C6 glioma tumour cells were implanted on irradiated CA Ms, there was a significant increase in the angiogenesis induced by tumour cells, compared to that in non-irradiated CAMs. Therefore, although X-rays have an initial inhibitory effect on angiogenesis, their action on the ECM enhances new vessel formation induced by glioma cells implanted on the tiss ue. (C) 2001 Wiley-Liss, Inc.