Differential expression of a truncated form of the urokinase-type plasminogen-activator receptor in normal and tumor thyroid cells.
We studied the urokinase-type plasminogen activator (uPA) receptor (uPA-R) in normal and neoplastic human thyroid cells. It has recently been shown that cleaved forms of uPA-R display an extremely strong chemotactic activity. Normal human thyroid TAD-2 cells express the intact form of the uPA-R and a truncated form lacking the uPA-binding domain on their surface, in a similar manner to tumor thyroid cell lines. However, in tumor thyroid cell lines, the amount of the truncated form is variable: high in papillary carcinoma cells, very low in follicular carcinoma cells, and not detectable in anaplastic carcinoma cells. Similar studies on primary cell cultures confirm the presence of the truncated form of uPA-R in normal and in papillary carcinoma cells and its partial or total loss in follicular carcinoma cells. The presence of truncated uPA-R correlates to uPA secretion, except in papillary carcinoma cells, which express the truncated form of uPA-R but do not release uPA. uPA-R is also able to act as an adhesion receptor by binding vitronectin (VTN) and interacting with integrins. We observe that removal of uPA-R from the surface of normal thyroid and anaplastic carcinoma cells by phosphatidylinositol-specific phospholipase C or treatment with anti-uPA-R antibodies decreases the adhesion of both cell types to VTN and, less efficiently, to fibronectin or collagen. On the other hand, uPA treatment strongly increases the adhesion of anaplastic carcinoma cells specifically to VTN.
Ragno
P
P
Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy.
Montuori
N
N
Covelli
B
B
Hoyer-Hansen
G
G
Rossi
G
G
D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator