Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice.
Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies.
Jost
Maud
M
Laboratory of Tumor and Developmental Biology, Center for Experimental Cancer Research, Center for Biomedical Integrative Genoproteomics, University of Liège, Tour de Pathologie (B23), Sart-Tilman, B-4000 Liège, Belgium.
Folgueras
Alicia R
AR
Frérart
Françoise
F
Pendas
Alberto M
AM
Blacher
Silvia
S
Houard
Xavier
X
Berndt
Sarah
S
Munaut
Carine
C
Cataldo
Didier
D
Alvarez
Jesus
J
Melen-Lamalle
Laurence
L
Foidart
Jean-Michel
JM
López-Otín
Carlos
C
Noël
Agnès
A
D000818:Animals; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D007797:Laminin; D008297:Male; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology; D011509:Proteoglycans; D012878:Skin Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19