Vascularization of tumors: a review

Abstract

It is apparent that tumors excite a vascular response that is generally greater than that seen with various other inciting factors. Epidermis appears to be capable of similar activity, whereas dermis does not. All the evidence so far obtained points to the presence of a diffusible factor inciting this reaction. It is now known that capillary budding in inflammatory and healing tissues is a accompanied by mitotic activity in endothelial cells and it would appear only logical to believe that a similar activity must accompany vascularization of tumors which indeed has been demonstrated to be the case. However, vascularization is a complex phenomenon and requires not only mitotic stimulation but various other changes that are not all defined. In spite of considerable work to quantify the vascular responses seen under various conditions, one must conclude objectively that none of the methods in current use are entirely satisfactory. In addition, the variations in methods employed, ranging from the use of the chick chorioallantoic membrane to the hamster cheek pouch, introduce many variables into this already complicated picture. Attempts to identify the specific chemical factor(s) responsible for the vascularization of tumors and/or other tissues have involved considerable efforts but have not so far succeeded in identifying a specific chemical. Questions of specificity, of quantitative rather than qualitative differences between tumors and other tissues, still remain. However, it is unquestionable that it is logical to attempt to identify the factor(s) involved and that this area of investigation provides one of the few straightforward approaches to the study of tumor therapy. Inhibition of tumor angiogenic factors appears to be a real possibility and should be continued. There would appear to be little doubt that there is considerable variation between different tumors in the stroma and vascular responses that they induce. Particularly striking is the fact that certain tumors can receive their blood supply via channels composed of tumor cells rather than through blood vessels lined with endothelium. This finding could certainly explain differences in radiosensitivity. It is most important that a variety of different tumors be examined for their vascular and stromal responses and that our present knowledge be enlarged to cover many other tumors. This entire field of activity is dependent upon technological advances. The three methods described for the study of vascularization—the hamster cheek-pouch chamber, the chorioallantoic membrane, and the cornea—are all considerable advances over past methods but none can be said to be free from undesirable complications nor amenable to adequate quantification. It is most important that new methods for the study of this phenomenon be sought. It is surprising not that some discrepant results have occurred, but rather that there are not many more.