EXPRESSION OF STEM-CELL FACTOR AND ITS RECEPTOR C-KIT PROTEIN IN NORMAL TESTICULAR TISSUE AND MALIGNANT GERM-CELL TUMORS

The proto-oncogene c-kit and its ligand stem-cell factor (SCF) may pla y an important role in the development of normal and malignant testicu lar tissue. This study investigates the presence of SCF and c-kit prot ein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non- seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an imm unohistochemical approach. Out of 9 testicular cancer specimens classi fied as pure seminomas, 7 (78%) showed a strong immunohistochemical re action for both SCF and c-kit protein on the surface of the tumour cel ls. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit protein and only faint positivity was found in 6 tumours (26%). Differentiated ter atomatous structures within the specimens of nonseminomatous tumours s howed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCE No se cretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cel l lines in culture conditions without fetal calf serum resulted in a 1 .4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultu red in serum-containing media. In the normal testicular tissue the ger m-cells displayed a Introduction strong immunohistochemical reaction f or c-kit protein while SCF positivity was found at the tubular membran e and on the surface of Sertoli cells. The SCF/c-kit system may posses s a regulatory function in normal testicular tissue by possibly provid ing the microenvironment necessary for spermatogenesis. With the devel opment of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growth stimulato ry effect of high concentrations of SCF on nonseminomatous testicular cancer cell lines can be detected only in culture conditions with seru m-free media. The effects achievable by the combination of SCF with ot her growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its pos sible implications for the understanding and treatment of male inferti lity.