Implications of adrenomedullin expression in the invasion of squamous cell carcinoma of the uterine cervix.

Abstract

Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including vasodilatation, growth regulation, and carcinogenesis. To elucidate the possible role of AM in the growth and invasion of uterine cervical carcinoma, the presence and distribution of AM and AM mRNA was examined in the neoplastic changes of squamous epithelium of the uterine cervix. The expression of AM mRNA by CaSki, a uterine squamous cell carcinoma cell line, was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The presence and distribution of AM and AM mRNA in sections of normal cervical tissues, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinomas were evaluated by immunohistochemical staining with a specific antibody against AM and by in situ RT-PCR, respectively. AM mRNA expression in CaSki cells was demonstrated by RT-PCR. Immunohistochemical staining for AM and in situ RT-PCR revealed that AM and AM mRNA were expressed in invasive squamous carcinoma cells, but not in normal cervical epithelium or in CIN lesions. Abundant expression of AM and AM mRNA was localized in the cytoplasm of carcinoma cells of bulky invasive carcinomas, while in early invasive carcinoma, the expression of AM and AM mRNA was more prominent in stromal cells adjacent to the early invasive carcinoma cells than in the carcinoma cells themselves. Because AM expression was evident only in invasive cervical squamous carcinoma cells and the stromal cells adjacent to early invasive carcinomas, it is likely that AM may play an important role in the growth and invasion of squamous cell carcinoma of the uterine cervix.