Do tumor vessels regress?

Posted on Thu, 09/18/2014 - 2:37pm by Nagy, John D

Do tumor vessels regress?

Yes, despite a remarkably durable contrary dogma. Evidence exists, and has for decades, that neovessels regress in the absence of growth factor support, and in fact mature vessels can also regress. Here's one passage from a 1999 abstract from Holash, Wiegand and Yancopoulos (1999; New Model of Tumor Angiogenesis: Dynamic Balance Between Vessel Regression and Growth Mediated by Angiopoietins and VEGF. Oncogene 18:5356--5362):

"Our analyses in several different tumor settings challenge the prevailing view that malignancies and metastases generally initiate as avascular masses that only belatedly induce vascular support. Instead, we find that malignant cells rapidly coopt existing host vessels to form an initially well-vascularized tumor mass. Paradoxically, the coopted vasculature does not undergo angiogenesis to support the growing tumor, but instead regresses (perhaps as part of a normal host defense mechanism) via a process that involves disruption of endothelial cell/smooth muscle cell interactions and endothelial cell apoptosis. This vessel regression in turn results in necrosis within the central part of the tumor." [Italics added]

Holash et al. show regression of existing, mature vessels in situ in a living mouse, challenging the apparently still prevalent idea that mature vasculature is static. Further, in our angiogenesis model, most of the vessels are not fully mature, and it is well-known that such neovessels are susceptible to regression on removal of growth factor support (see chapter 4 in Reza Forogh [ed] (2006; New Frontiers in Angiogenesis) written by Nicosia, Zhu and Aplin (Regulation of Postangiogenic Vascular Regression, pp. 79-95). This observation, and others, imply the regression term in the microvessel equation of our model. It's also important to note that this regression term does not depend on angiogenic signaling (and that VEGF is not the only angiogenic factor, nor is its translation the only energetic cost associated with the angiogenic signal).

To the lab members, I would like to remind you of something that I recently forgot. Whenever we present or publish, we can never count on a sympathetic audience. That's a good thing. It requires us to prepare all communications with exquisite care. Especially before giving a talk, we must have all details of our previous work and results from earlier studies available for immediate recall, even if we feel they are well-established. We will be challenged, perhaps more than most. Only by thorough preparation can we defend our work effectively and professionally. Our work is worth defending.