Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human carcinomas, stromelysin-3/matrix metalloproteinase 11 (ST3, MMP11) expression by nonmalignant fibroblastic cells located in the immediate vicinity of cancer cells is a bad prognostic factor. Using mouse models of primary tumors, it has been demonstrated that ST3 is a key player during local invasion, favoring cancer cell survival in connective tissue through an antiapoptotic function. To investigate the ST3 impact on additional phases of cancer cell invasion, we developed mammary gland cancer prone MMTV-ras transgenic mice in wild-type (ras+/+;ST3+/+) or ST3-deficient (ras+/+;ST3-/-) genotype and studied their whole natural cancer history. The tumor-free survival and delay between the first ras oncogenic hit and primary tumor appearance increased in ras+/+;ST3-/- mice (P < 0.000001 and <0.0000007, respectively). A systematic search for occult primary tumors and metastases revealed, in addition to a lower total number and size of primary tumors (P < 0.02), an unexpected higher number of metastases (P < 0.01) in ras+/+;ST3-/- mice. Moreover, for a similar number and size of primary invasive tumors, ras+/+;ST3-/- mice developed more metastases, indicating that the cancer cells evolving in ST3-deficient stroma have an increased potential to hematogenous dissemination. We conclude that the ST3 microenvironment is a consistently active partner of invading cancer cells but that its function differs throughout cancer progression, being tumor enhancer or repressor in processes leading to local or distal invasion. Such a dual effect for an MMP might shed light, at least partially, for the absence of survival benefit for patients included in anti-MMP clinical trials.
 ...
PMID:Dual stromelysin-3 function during natural mouse mammary tumor virus-ras tumor progression. 1452 8

Epiblast cells in the early chick embryo differentiate to form all three germ layers through ingression of cells at the primitive streak across the basement membrane that underlies the epiblast. We tested the idea that degradation of the extracellular matrix components by matrix metalloproteinase(s) (MMPs) is involved in this process. Epiblast cells and primitive streak cells were dissociated into single cells and seeded onto a reconstituted basement membrane gel in vitro. Following overnight culture, approximately half the cells made holes in the substratum by dissolving the gel matrix. This invasive phenomenon was reproduced in vitro even when the cells were cultured upside down using a hanging culture system. We detected gelatinase activity in the culture supernatants from both prestreak epiblast cells and primitive streak cells. Pro-MMP-2 was detected in the culture media of the prestreak/streak cells as a 72-kDa band by gelatin zymography. In RT-PCR experiments, mRNAs for MMP-2, membrane-type (MT)3-MMP and MMP-11(stromelysin-3) were expressed in the epiblast cells before and during primitive streak formation. Injection of GM 6001 or other MMP inhibitors into the subgerminal cavity of the embryo inhibited the formation of the primitive streak and/or the primitive groove in more than 82% of the injected embryos. On the other hand, injection of a negative control compound instead of GM 6001 did not cause substantial inhibition. These results suggest that MMPs are involved in the enzymatic degradation of the basement membrane underlying the epiblast and are thus important for the ingression of mesendodermal cells along the primitive streak.
 ...
PMID:Invasion by matrix metalloproteinase-expressing cells is important for primitive streak formation in early chick blastoderm. 2016 Apr 29


<< Previous 1 2 3