Ectopic expression of KLK6 in MDA-MB-435 melanoma cells reduces tumorigenicity in vivo

Melanoma is an aggressive form of cancer with poor prognosis therefore, identification of associated pathophysiological mechanisms is imperative towards the development of new therapeutic strategies. The KLK6 is a serine protease normally expressed in the epidermis. Recently, we found that eliminati...

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Published in:Pathology, research and practice research and practice, 2021-01, Vol.217, p.153276-153276, Article 153276
Main Authors: Pampalakis, Georgios, Zingkou, Eleni, Zoumpourlis, Vassilis, Sotiropoulou, Georgia
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms
Cell Line, Tumor
Enzyme Induction
Female
Gene Expression Regulation, Neoplastic
Human kallikrein-related peptidase 6 (KLK6)
Humans
Kallikreins - biosynthesis
Kallikreins - genetics
MDA-MB-435
Melanoma
Melanoma - enzymology
Melanoma - genetics
Melanoma - pathology
Mice
Mice, SCID
Signal Transduction
Skin Neoplasms - enzymology
Skin Neoplasms - genetics
Skin Neoplasms - pathology
TGF-β
Tumor Burden
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Summary:Melanoma is an aggressive form of cancer with poor prognosis therefore, identification of associated pathophysiological mechanisms is imperative towards the development of new therapeutic strategies. The KLK6 is a serine protease normally expressed in the epidermis. Recently, we found that elimination of Klk6 in mice results in enhanced resistance to chemically induced non-melanoma skin cancer. To delineate putative roles of KLK6 in melanoma, the invasive KLK6-non-expressing MDA-MB-435 melanoma cell line was stably transfected with the full-length KLK6 cDNA and expression of the corresponding RNA and protein were confirmed. Interestingly, restoration of KLK6 expression resulted in markedly suppressed growth of primary tumors when orthotopically implanted in SCID mice. Analysis of data retrieved from the human protein atlas revealed that melanomas with high KLK6 expression have a trend for longer survival. Collectively, we suggest that KLK6 inhibits growth of melanomas.
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2020.153276