Angiotensin-converting enzyme (CD143) in neoplastic germ cells

Angiotensin I-converting enzyme (ACE, CD143, Kininase II, EC 3.4.15.1) occu rs in two isoforms; whereas the somatic isoform (sACE) appears in certain e ndothelial cells and some other cell types, the testicular isoform (tACE) w as found in humans and various mammals only during spermiogenesis. An expre ssion of ACE was reported formerly in some human seminomas, but its isoform type, cellular distribution, and pathogenetic meaning are not known. There fore we analyzed normal human testes, 22 different testicular tumors, and 2 3 fetal and postnatal tissues of different stages of testicular development . By reverse transcriptase-polymerase chain reaction, ACE mRNA isoforms wer e assessed in homogenized tissue sections and in germ cells selectively iso lated by laser-assisted cell picking. Immunohistochemistry was performed on consecutive sections using monoclonal antibodies specific to the human som atic isoform or both, sACE and tACE. In adult men, tACE was detectable in s permatids and spermatozoa, but normal spermatogonia and spermatocytes were not found to express ACE in any isoform. By contrast, both mRNA and protein of sACE were detectable in the cells of intratubular germ cell neoplasm, s eminomas, and other testicular tumor types. Because sACE was also found in fetal germ cells, our findings point to profound differences in the regulat ion or ACE expression in fetal, mature adult, and neoplastic germ cells. Th ey are in agreement with the concept that neoplastic germ cells phenotypica lly reflect an embryonic stage of cellular differentiation. Laser-assisted cell picking proved to be a reliable method to investigate differently regu lated mRNA of cells which reside in close neighborhood within complex tissu es.