NDLI: Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Content Provider	PubMed Central
Author	Srivastava, Ajay Carlos, Pastor-pareja Jose Igaki, Tatsushi Pagliarini, Raymond Xu, Tian
Copyright Year	2007
Abstract	Organ and tissue integrity is often maintained in animals by a specialized extracellular matrix structure called the basement membrane (BM). Accumulated evidence indicates that BM remodeling occurs during development and tumor invasion. Although the BM organizes and functions at the organ level, most past studies have explored its biochemical and in vitro properties. In this study, we monitor the BM in vivo during developmental tissue invasion for disc eversion and tumor invasion in Drosophila and modulate BM integrity with genetic alterations affecting either the whole organism or the targeted discs or tumors. We observe that the degradation of BM by the discs or the tumors is an early event during invasion processes and that preventing BM degradation completely blocks both tissue and tumor invasion, indicating that modulation of BM is essential for developmental and tumor invasion. Furthermore, elements of the invasion machinery, including JNK-induced matrix metalloproteinase (MMP) expression, are shared by both disc eversion and tumor invasion processes. Moreover, we show that although expression of MMP inhibitor, TIMP, is sufficient to halt developmental invasion, inhibition of proteases by both TIMP and RECK are required to block tumor invasion. These data suggest that tumor cells have a more robust invasion mechanism and could acquire metastatic behavior by co-opting developmental invasion programs. This type of co-option may be a general feature contributing to the progression of tumors. Finally, although past efforts using MMP inhibitors have not yielded much success, our results strongly argue that BM modulation could be a critical target for cancer therapy.
Related Links	http://dx.doi.org/10.1073/pnas.0611666104
Ending Page	2726
Page Count	6
Starting Page	2721
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-02-20
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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