Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, an RGD-containing peptide isolated from the venom of Trimeresurus albolabris.
Albolabrin, a 7.5-kDa cysteine-rich protein isolated from the venom of Trimeresurus albolabris, contains the arginine-glycine-aspartic acid (RGD) cell recognition sequence found in many cell adhesion-promoting extracellular matrix proteins, such as fibronectin and laminin. Albolabrin belongs to a family of RGD-containing peptides, termed disintegrins, recently isolated from the venom of various vipers and discovered to be potent inhibitors of both platelet aggregation and cell-substratum adhesion. Here we report that albolabrin inhibited the attachment of B16-F10 mouse melanoma cells to either fibronectin or laminin absorbed on plastic. When immobilized on plastic, albolabrin promoted B16-F10 melanoma cell attachment; this was inhibited by either RGD-serine (RGDS) or antibodies to integrins, suggesting that albolabrin binds via its RGD amino sequence to integrin receptors expressed on the melanoma cell surface. In an in vivo experimental metastasis system, albolabrin at a concentration of 300-600 nM inhibited C57BL/6 mouse lung colonization by tail vein-injected mouse melanoma cells and was at least 2000 times more active than RGDS in this assay. We propose that albolabrin inhibits tumor cell metastasis by inhibiting integrin-mediated attachment of melanoma cells to RGD-containing components of the extracellular matrix in the mouse lung.
Soszka
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T
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096.
Knudsen
K A
KA
Beviglia
L
L
Rossi
C
C
Poggi
A
A
Niewiarowski
S
S
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003435:Crotalid Venoms / Q000737:chemistry*; D005353:Fibronectins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000503:physiopathology; D009842:Oligopeptides / Q000032:analysis; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D012910:Snake Venoms; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D003435:Crotalid Venoms; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; C064595:albolabrin; C047981:arginyl-glycyl-aspartic acid; C046617:arginyl-glycyl-aspartyl-serine