CALCITONIN GENE-RELATED PEPTIDE-IMMUNOREACTIVE NERVES IN CARCINOMA EXPERIMENTALLY INDUCED IN THE HAMSTER TONGUE

Innervation to carcinomas induced by 9,10-dimethyl-1,2-benzanthracene (DMBA) in the hamster tongue was investigated by means of immunohistochemistry for calcitonin gene-related peptide (CGRP). The application of DMBA induced papillomatous tumors with epithelial dysplasia and then well-differentiated squamous cell carcinomas showing cord-like invasion of the muscle layer developed under the papillomatous portion of the epithelium. The characteristic features of the innervation were the scarcity of CGRP-positive nerve fibers in the carcinomatous stroma and the loss of their relationships with blood vessels. In contrast, numerous fine CGRP-positive nerves which were associated with blood vessels and carcinoma nests were present in the carcinoma invading zone where infiltration of lymphocytes, neutrophils, mast cells and macrophages was recognized. In addition, a dense distribution of intensely immunopositive nerves was seen around arterioles in the invasion zone and in the surrounding muscle layer. The results indicate possible involvement of the CGRP-positive nerves in the dull pain associated with malignant tumors and cellular responses at the site of tumor invasion, and in providing sufficient blood supply to the tumor tissue which is devoid of autoregulatory mechanism of the blood flow.