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.
Molecular Endocrinology Laboratory, Laval University Hospital Center (CHUL), Laval University, Ste. Foy, Quebec, Canada.
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Sourla
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Doillon
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Koutsilieris
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