Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation

Fetal development and tumor progression both require a complex system of ex tracellular matrix (ECM) synthesis and breakdown, which is mediated by, for instance, the matrix metalloproteinases (MMPs). Human metalloelastase (MMP -12) is an MMP, the expression of which has so far been documented in macro phages associated with atherosclerosis, wound repair, and certain cancers. In this study we first examined the expression of MMP-12 during human fetal development. By in situ hybridization MMP-12 transcripts were detected in chondrocytes of hypertrophic cartilage in vertebrae of the spinal column, i n ribs, and in extremities undergoing ossification, beginning at the gestat ional age of 8 weeks. Also, periosteal cells expressed MMP-12 at 11 weeks. No expression of MMP-12 mRNA could be noted in other fetal tissues, includi ng the skin, lungs, intestine, kidney, and liver. Expression of MMP-12 mRNA could not be detected in adult normal cartilage or osteosarcomas, but in c hondrosarcomas both macrophages (8 of 19 samples) (identified by CD68 immun ostaining) and chondrosarcoma cells (8 of 19) were positive. MMP-12 was als o demonstrated in the tumors by western blotting and it was expressed in th e same regions as MMP-13 mRNA. By immunostaining, MMP-12 mRNA colocalized w ith the protein in both fetal and chondrosarcoma specimens. Unlike basic fi broblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta ), tumor necrosis factor-alpha (TNF-alpha) induced MMP-12 mRNA production i n chondrosarcoma-derived HTB-94 cells. Our results suggest that MMP-12 play s an important role in ECM remodeling during fetal bone development and is induced when chondrocytes undergo malignant transformation. (C) 2001 by Els evier Science Inc. All rights reserved.