Our results identify the tPA-LRP1 pathway as a key switch that drives melanoma progression, in part by modulating the cellular composition and proteolytic makeup of the tumor niche.
<i>In vivo</i>, coadministration of tPA improved the anticancer efficacy of nanoparticle-encapsulated paclitaxel in subcutaneous syngeneic mouse melanoma and orthotopic xenograft lung cancer models.
Decreased tissue plasminogen activator and increased plasminogen activator inhibitors and increased activator protein-1 and specific promoter 1 are associated with inhibition of invasion in human A375 melanoma deprived of tyrosine and phenylalanine.
Scatchard analyses were performed using tPA molecules isolated from human melanoma and colon cells as well as from C127 and Chinese hamster ovary cells that had been transfected with the human tPA gene.
The Fibrinolysis Subcommittee of the International Committee for Thrombosis and Haemostasis recommended the melanoma source t-PA (86/670) as the next I.S. in order to maintain continuity with the 1st I.S. which was also a melanoma-type preparation.