Matrix Metalloproteinase-19 Is Expressed in Myeloid Cells in an Adhesion-Dependent Manner and Associates with the Cell Surface

Abstract

We have previously reported the isolation of the human matrix metalloproteinase (MMP)-19 (also referred to as RASI) from a synovium of a patient suffering from rheumatoid arthritis and its expression at the cell surface of activated PBMC. In this study, we have analyzed the regulation and cell surface expression of human MMP-19 in several human cell lines and blood-derived cells. Among the cell lines analyzed, MMP-19 is largely expressed by lung fibroblasts as well as by myeloid cell lines THP-1 and HL-60. After fractionating PBMC into CD14− and CD14+ populations we found that only the latter one expresses MMP-19. Although the myeloid cell lines as well as CD14+ cells express MMP-19 without stimulation, its production can be up-regulated by phorbol esters (PMA) or by adhesion. The adhesion-dependent expression was down-regulated or even abrogated by blockade of adhesion or interfering with adhesion-controlling signaling using α-tocopherol. We have shown that MMP-19 associates with the cell surface of myeloid cells. This cell surface association was not affected by phospholipase C. However, acidic treatment of the THP-1-derived cell membranes abolished the immunoprecipitation of MMP-19 thereof. Moreover, a high salt treatment of THP-1 cells diminished the MMP-19 detection on the cell surface. This implicates a noncovalent attachment of MMP-19 to the cell surface. Because a truncated form of the MMP-19, in which the hemopexin-like domain was deleted (ΔhpMMP-19), does not associate with the surface, the hemopexin-like domain appears to be critical for the cell surface attachment of human MMP-19.

Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

“…Both matrix metalloproteinases (15 and 19) were expressed by stromal fibroblasts in high percentage and by macrophages in smaller amounts, which is in accordance with previous data on cell types expressing MMP-19 (28,29). Several studies using mouse models of genetically altered fibroblasts demonstrated a direct involvement of resident fibroblasts in the onset of cancer (30); moreover, both genetic and cell-biology studies indicate that tumor growth is not just determined by malignant cancer cells themselves, but also by the tumor stroma (31).…”

Matrix metalloproteinase‐19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation

“…In tissue samples, TNF-␣ protein was expressed in the keratinocytes adjacent to MMP-19-positive cells. The fact that TNF-␣ induces adhesion molecules and that it stimulates MMP-19 could also suggest that MMP-19 is a reconstructive enzyme in the repair of destroyed BM and that cell adhesion might have an effect on its expression, as shown in myeloid cells 40 or by comparing to the presence of E-cadherin. However, caution is needed when extrapolating results from cell culture to tissue in vivo since, based on transgenic mouse studies, many cytokines have different effects on keratinocytes in vivo and in culture.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…In this respect, consistent evidences highlight a role in the modulation of cell motility even under physiological conditions: degradation of laminin is associated to promotion of epithelial cells as well as keratinocytes migration and proliferation (Sadowski et al, 2003(Sadowski et al, , 2005. Myeloid cells and T-lymphocytes efficiently compartmentalize the enzyme at their leading edge through interaction with unknown cell surface molecules, to improving extravasation and migration toward the flogistic site (Beck et al, 2008;Mauch et al, 2002). Additional evidence of a positive influence of MMP-19 in tumor growth come from studies in vitro on breast cancer cells where siRNA-mediated inhibition of the enzyme down-regulates tumor invasiveness (Hegedüs et al, 2008).…”