Protein synthesis is required for laminin-induced expression of the 67-kDa laminin receptor and its 37-kDa precursor.
The high affinity 67-kDa laminin receptor (67LR) is highly expressed in metastatically active human cancers. A 37-kDa polypeptide has been identified as its precursor (37LRP). Antibodies raised against 37LRP-derived synthetic peptides were used in immunogold electron microscopy and immunoblot studies to assess the effect of laminin on expression of the 67LR and the 37LRP. Laminin (15 micrograms/ml) treatment of suspended A2058 human melanoma cells doubled the expression of both 37LRP and the 67LR. Fibronectin had no effect. There was no effect of laminin on the expression of actin or galectin-3. Cycloheximide treatment of cells prior to laminin abrogated its inducible effect. The results suggest that binding of laminin by cell surface laminin receptors induces synthesis of the 37LRP and mature 67LR, with a consequent delivery to the cell surface of more laminin binding proteins for potentiated attachment of the melanoma cell to the basement membrane during invasion and metastasis.
Romanov
V I
VI
Membrane Biology Section, NCI-Frederick Cancer Research and Development Center, MD 21702.
Wrathall
L S
LS
Simmons
T D
TD
Pinto da Silva
P
P
Sobel
M E
ME
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007797:Laminin / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011498:Protein Precursors / Q000378:metabolism; D017474:Receptors, Laminin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D007797:Laminin; D011498:Protein Precursors; D017474:Receptors, Laminin; D003513:Cycloheximide