Centripetal spread of endothelial cell mitotic activity in the artery leading to a rapidly growing tumor

Vascular proliferation and growth have been attributed either to biophysical forces in the vessel lumen or to chemical mediators. In this study growth and endothelial cell tritiated thymidine uptake in the spermatic artery of the rat during early growth of the Walker 256 carcinoma in the testicle were examined. Testicular blood flow was measured with radioactive microspheres; radioautography following administration of tritiated thymidine was employed to define the endothelial cell labeling index; angiography was employed to assess the diameter of the spermatic artery lumen; and the mass of the artery was determined directly. Endothelial proliferation in the spermatic artery was increased on the second day, simultaneous with rather than subsequent to a significant increase in blood flow to the testicle. Moreover, endothelial cell thymidine uptake began to decline well before the blood flow through the artery reached a maximum. A gradient in endothelial cell proliferation and in lumen diameter of the spermatic artery became apparent during tumor growth; the increase in both lumen diameter and endothelial cell thymidine uptake in the spermatic artery occurred first in the portions nearest the testicle and spread centripetally throughout the length of the artery over several days. Because the spermatic artery is an end artery, without branches and without a normal change in internal diameter, and because the increase in blood flow must have occurred throughout the length of the artery at the same time, we conclude that factors other than those related to an increase in blood flow were primarily responsible for the increase in endothelial cell turnover. These observations make a chemical messenger, perhaps moving retrogradely through cell-to-cell contact, the most likely candidate as the responsible mediator.