Three-dimensional type I collagen gel system for the study of osteoblastic metastases produced by metastatic prostate cancer.
We developed a three-dimensional type I collagen gel cell culture system that allows coculturing of human MG-63 osteoblast-like cells and various human cancer cells. Inoculation of human PC-3 metastatic prostate cancer cells into this type I collagen gel containing human MG-63 osteoblast-like cells produced an osteoblastic-like reaction that presented as an increased number of MG-63 cells and increased density of type I collagen around MG-63 cells adjacent to inoculated PC-3 cells by microscope analysis. Under identical experimental conditions, inoculation of cell-free medium, human KLE endometrial adenocarcinoma cells, and Calu-1 lung cancer cells did not produce this blastic-like reaction. In situ hybridization documented the uniform expression of insulin-like growth factor I (IGF-I) and of urokinase-type plasminogen activator (uPA) mRNA in MG-63 and PC-3 cells separately cultured in this substrata. The uniform expression of uPA was also documented by immunocytochemistry using a monoclonal and a polyclonal antihuman uPA antibody. The relative expression of uPA was higher in PC-3 cells than in MG-63, KLE, and Calu-1 cancer cells. We conclude that this novel cell culture system may become a useful model to study the pathophysiology of the osteoblastic reaction in vitro.
Koutsilieris
M
M
Molecular Endocrinology Laboratory, Hospital Center Laval University (CHUL), St. Foy, Quebec, Canada.
Sourla
A
A
Pelletier
G
G
Doillon
C J
CJ
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D005782:Gels; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000473:pathology* / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
D005782:Gels; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator