PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.
Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients.
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Maya
M
Zigler
Takafumi
T
Kamiya
Emily C
EC
Brantley
Gabriel J
GJ
Villares
Menashe
M
Bar-Eli
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation; D002448:Cell Adhesion; D002465:Cell Movement; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008545:Melanoma / Q000097:blood / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000556:secondary / Q000628:therapy; D051379:Mice; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009360:Neoplastic Cells, Circulating; D010641:Phenotype; D034741:RNA, Small Interfering / Q000627:therapeutic use; D044463:Receptor, PAR-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology; D013917:Thrombin / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D044463:Receptor, PAR-1; D013917:Thrombin