Laminin binding in membranes of a rat pancreatic acinar cell line are targets for glucocorticoids.
The adhesive properties of tumor cells to basement membranes are known to play a crucial role in the complex process of tumor invasion and metastasis. Therefore, the interaction between the rat pancreatic acinar cell line AR42J and various extracellular matrix components along the route of differentiation induced by glucocorticoids was investigated. AR42J cells displayed a significantly higher affinity to laminin than to type IV collagen and fibronectin. Flow cytometric analysis showed expression of the 67-kilodalton laminin receptor and the integrin VLA-6 as potential laminin binding proteins in AR42J cells. Cell adhesion inhibition studies revealed that binding of undifferentiated AR42J cells to laminin was mediated predominantly by the 67-kilodalton laminin receptor. Dexamethasone pretreatment, which results in a more differentiated phenotype of AR42J cells, reduced the adhesion to laminin. In contrast to undifferentiated cells, interaction of differentiated AR42J cells to laminin was mediated by VLA-6. Dexamethasone-induced differentiation of pancreatic AR42J cells was paralleled by a decreased expression of 67-kilodalton laminin receptors, most likely because of a downregulation of the steady-state concentration of 67-kilodalton laminin receptor messenger RNA induced by dexamethasone. The hormonal modulation of cell matrix interactions opens interesting perspectives to the potential regulation of infiltrative growth and metastasis in pancreatic cancer.
Stallmach
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A
Abteilung für Innere Medizin mit Schwerpunkt Gastroenterologie, Klinikum Steglitz, Freie Universität Berlin, Germany.
Rosewicz
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S
Kaiser
A
A
Matthes
H
H
Schuppan
D
D
Riecken
E O
EO
D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism* / Q000502:physiology; D008970:Molecular Weight; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011971:Receptors, Immunologic / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D017474:Receptors, Laminin
D005938:Glucocorticoids; D016023:Integrins; D007797:Laminin; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017474:Receptors, Laminin