Activation of metalloproteinases-2 and -9 by interleukin-1alpha in S100A4-positive liposarcoma cell line: correlation with cell invasiveness.
BACKGROUND
The S100A4 gene may affect the invasive properties of tumor cells through modulation of metalloproteinases (MMPs) and their inhibitors (TIMPs).


METHODS
In the human liposarcoma cell line, SW872, we analyzed the expression of S100A4 protein by immunohistochemistry and flow cytometry. The production of MMP2, MMP9, TIMP1 and TIMP2 was assessed by gelatin zymography and enzyme-linked immunoabsorbent assay before and after interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) stimulation; cell invasiveness was measured by Matrigel invasion assay.


RESULTS
S100A4-positive SW872 cells responded to IL-1alpha with induction of immunoreactive MMP2 and TIMP1 and with activation of both MMPs, the latter significantly associated with an increase of cell invasiveness. Treatment with IL-6 induced less significant variations resulting in a more stable invasive behavior.


CONCLUSIONS
These data show that S100A4-positive SW872 respond to interleukins by influencing the behavior of factors involved in extracellular matrix degradation and emphasize the predominant role of MMP activity status on the positive regulation of cell migration mechanisms.
Pazzaglia
Laura
L
Department of Muscoloskeletal Oncology, Rizzoli Orthopaedic Institute, 40100, Bologna, Italy.
Ponticelli
Francesca
F
Magagnoli
Giovanna
G
Magagnoli
Giorgia
G
Gamberi
Gabriella
G
Ragazzini
Paola
P
Balladelli
Alba
A
Picci
Piero
P
Benassi
Mariaserena
M
D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008080:Liposarcoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C077591:S100A4 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9