The role of human tissue kallikreins 7 and 8 in intracranial malignancies.
Recent evidence suggests that many tissue kallikreins are implicated in carcinogenesis. Kallikrein 8 (KLK8) plays a role in the physiology of the central nervous system. Kallikrein 7 (KLK7) takes part in skin desquamation. Both show altered expression in ovarian and breast cancer. In this study, we examined the level of mRNA expression of the KLK7 and KLK8 genes in 73 intracranial tumors using qualitative RT-PCR. The results were correlated with clinical and histomorphological variables and patient outcome. The expression of both genes was also examined in the brain cancer cell lines U-251 MG, D54 and SH-SY5Y and the invasive capacity of glioblastoma cells U-251 MG overexpressing hK7 or hK8 was also investigated in an in vitro Matrigel assay. Follow-up analysis revealed that expression of KLK7 mRNA was associated with shorter overall survival (OS) compared to patients with no KLK7 expression, as determined by Cox proportional hazard regression analysis. Overexpression of hK7 protein by cultivated brain tumor cells significantly enhanced the invasive potential in the Matrigel invasion assay, in contrast to cells overexpressing hK8 protein. Our data suggest that hK7 protein overexpression is associated with a more aggressive phenotype in brain cancer cells.
Prezas
Panagiotis
P
G. Papanicolaou Research Center of Oncology, Saint Savas Hospital, 171 Alexandras Avenue, GR-11522 Athens, Greece.
Scorilas
Andreas
A
Yfanti
Christina
C
Viktorov
Petar
P
Agnanti
Niki
N
Diamandis
Eleftherios
E
Talieri
Maroulio
M
D000328:Adult; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D017931:DNA Primers; D006801:Humans; D008875:Middle Aged; D020840:Tissue Kallikreins / Q000502:physiology*
D017931:DNA Primers; D020840:Tissue Kallikreins