Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells.
We inoculated the KLE human endometrial cancer, MCF-7 and ZR-75 human breast cancer, and PC-3 human prostate cancer cells into three-dimensional type I collagen gel system that contained uniformy dispersed MG-63 osteoblast-like cells. Then, we analyzed the morphological evidence of osteoblasts reaction, local invasion around the inoculated cancer cells and expression of the cathepsin D and urokinase-type plasminogen activator (uPA) around the sites of inoculation using immunocytochemistry. The prostate cancer cells produced morphological evidence of blastic reaction presented as an increased number of MG-63 osteoblasts and increase density of type I collagen around the sites of inoculation with PC-3 cells. The inoculated MCF-7 and ZR-75 cells decreased the density of type I collagen and number of osteoblasts and invaded the collagen gel around the sites of inoculation. The KLE endometrial cancer cells and cell-free media produced no reaction at the inoculation sites suggestive of cancer cell-specific interactions with osteoblasts in this system. The expression of uPA was remarkably higher at the inoculation sites of PC-3 cells as compared with those of the other cancer cells. Cathepsin D expression was higher at the sites of inoculation with KLE, MCF-7 and PC-3 cancer cells. MG-63 osteoblasts contained relatively low expression of uPA and cathepsin D. We conclude that this collagen gel system is a useful model for studying the morphological evidence of local invasion and osteoblasts reaction produced in response to local growth of metastatic cancer cell in vitro.
Sourla
A
A
Molecular Endocrinology Laboratory, Laval University Hospital Center (CHUL), Laval University, Ste. Foy, Quebec, Canada.
Doillon
C
C
Koutsilieris
M
M
D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D002402:Cathepsin D / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D010006:Osteoblasts; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D009363:Neoplasm Proteins; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D