Expression and function of receptors for extracellular matrix proteins in human ductal adenocarcinomas of the pancreas.
Extracellular matrix proteins (ECM) may influence cellular differentiation via their receptors, the integrins. We recently presented evidence that ductal adenocarcinomas of the pancreas are able to produce ECM in vitro and in vivo (Br J Cancer 1994;49:144-51). This study examines whether pancreatic carcinoma cells are able to interact with ECM by expressing functionally active integrins. In eight human pancreatic tumor cell lines (AsPC-1, BxPC-3, CAPAN-1 and -2, PANC, PaTu-2, -3, and -44) and six xenografted tumors RNA and protein expression of integrin subunits alpha 5 (fibronectin receptor), alpha 6 (laminin receptor), and alpha V (vitronectin receptor) was investigated. In addition, alpha 1-alpha 6 and alpha V as well as beta 1-beta 4 were studied by fluorescence-activated cell sorter analysis. Integrin function was tested by attachment assays. alpha 2, alpha 3, alpha 5, alpha 6, and alpha V as well as beta 1, beta 3, and beta 4 were expressed, at both the RNA and the protein level, by all pancreatic tumors in vitro and in vivo. The tumor cell lines showed dose dependent adhesion to collagen, fibronectin, and laminin. Integrin expression could be modulated in part by serum depletion. None of the tumors showed alpha 1, alpha 4, and beta 2. Tumor cell differentiation or production of ECM was not correlated with integrin expression. Pancreatic ductal adenocarcinomas express a certain pattern of functionally active integrins that enable interaction with most matrix proteins, e.g., collagen, fibronectin, and laminin. Pancreatic adenocarcinomas possess both the ligands and the receptors of the extracellular matrix network. We speculate that through both classes of molecules, the tumor cells may bind to fibroblasts and probably stimulate their growth. However, it remains unclear whether and how integrin-ECM interaction exerts an influence on tumor cell differentiation.
Löhr
M
M
Department of Medicine, University of Rostock, Germany.
Trautmann
B
B
Göttler
M
M
Peters
S
S
Zauner
I
I
Maier
A
A
Klöppel
G
G
Liebe
S
S
Kreuser
E D
ED
D000818:Animals; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D016023:Integrins; D012313:RNA