Members of the tissue kallikrein‐related peptidase (KLK) family not only regulate several important physiological functions, but aberrant expression has also been associated with various malignancies.,Clinically, KLKs have been suggested as promising biomarkers for diagnosis and prognosis in many types of cancer.,As of yet, expression of KLKs and their role in skin cancers are, however, poorly addressed.,Malignant melanoma is an aggressive disease associated with poor prognosis.,Hence, diagnostic biomarkers to monitor melanoma progression are needed.,Herein, we demonstrate that although mRNA of several KLKs are aberrantly expressed in melanoma cell lines, only the KLK7 protein is highly secreted in vitro.,In line with these findings, ectopic expression of KLK7 in human melanomas and its absence in benign nevi were demonstrated by immunohistochemistry in vivo.,Interestingly, overexpression of KLK7 induced a significant reduction in melanoma cell proliferation and colony formation.,Moreover, KLK7 overexpression triggered an increase in cell motility and invasion associated with decreased expression of E‐cadherin and an upregulation of MCAM/CD146.,Our results demonstrate, for the first time, that aberrant KLK7 expression leads to a switch from proliferative to invasive phenotype, suggesting a potential role of KLK7 in melanoma progression.,Thus, we hypothesize that KLK7 may represent a potential biomarker for melanoma progression.
Tumor spreading is associated with the degradation of extracellular matrix proteins, mediated by the overexpression of matrix metalloproteinase 9 (MMP-9).,Although, such overexpression was linked to epigenetic promoter methylation, the role of intragenic methylation was not clarified yet.,Melanoma was used as tumor model to investigate the relationship between the DNA intragenic methylation of MMP9 gene and MMP-9 overexpression at transcriptional and protein levels.,Computational analysis revealed DNA hypermethylation within the intragenic CpG-2 region of MMP9 gene in melanoma samples with high MMP-9 transcript levels.,In vitro validation showed that CpG-2 hotspot region was hypermethylated in the A375 melanoma cell line with highest mRNA and protein levels of MMP-9, while low methylation levels were observed in the MEWO cell line where MMP-9 was undetectable.,Concordant results were demonstrated in both A2058 and M14 cell lines.,This correlation may give further insights on the role of MMP-9 upregulation in melanoma.