Abstract
The autonomic nerve fibers distributed in the walls of blood vessels maintain an adequate blood distribution and supply to the whole body. The growth of malignant tumors is also considered to be influenced by the degree of tumor vasculature, including nerve fiber distribution. When the tumor growth lacks adrenergic innervation, then it is assumed that such a state enhances the tumor growth. It is of great value to determine the relationship between tumor vasculature and the degree of innervation in order that the appropriate chemotherapy and angiography can be utilized and applied to patients with cancer.
To our knowledge, the work reported here is the first designed to determine whether or not there actually is an adrenergic innervation involved in tumor vasculature.
The tumors used in these experiments were Walker Carcinosarcoma 256, Yoshida sarcoma, AH 130, NG-induced stomach cancer and DMBA-induced mammary cancer in rats, and Sarcoma 180, Myeloma (MOPC 104 Tumor) in mice. Stomach, mammary and rectal cancer as well as Wilmus tumor were also examined as clinical materials. The fluorescent histochemical technique of Falck was employed for the detection of noradrenergic fluorescemce. For detection of the nerve endings along the tumor vasculature, Seto's modification of Bielschowskys' silver impregnation method was used. For the histochemical technique of determining monoamine oxidase activity and the chemical assay of catecholamine, Anton's method was employed.
The vasculature in the transplants of each tumor was demonstrated to be sinusoidal vessels in which noradrenergic fluorescence was absent. In the adjacent areas, however, where invasion of the tumor had not occurred, fluorescent fibers were demonstrated in the blood vessels. Catecholamines were not detected in the tumor tissues; and the nerve component around the tumor vasculature was absent. Thus it was evident that the adrenergic innervation in the sinusoidal vessels of experimental transplantable tumor, NGinduced stomach cancer and DMBA-induced mammary cancer is lacking. In the study of actual clinical cases, noradrenergic fluorescence in the vessels of stomach, rectal and mammary cancer tumors could not be demonstrated. Noradrenaline fluorescence tended to disappear in the normal appearing vasculature of the invaded area in cases of infiltration by NG-induced stomach cancer. MAO activities in both experimental and clinical tumors showed no clear cut tendency. The absence of vascular smooth muscle, the effector apparatus of adrenergic vasoconstriction may explain the lack of adrenergic innervation of the sinusoidal vasculatures. The results seen with the MAO activities cannot, however, explain the disappearance of adrenergic innervation of the vasculature of the invading tissue. Nerve destruction as a result of the tumor invasion has to be considered here.
Further studies are in progress concerning the lack of adrenergic innervation in the blood vessels in tumors.
