Hope for diseases like cancer with collagenase/MMP-9 dysfunction

We have discussed with you earlier in our blog that cytokines and their Inflammatory Cycle were critical to all disease proscesses. We have since gotten more specific and have shown that MMP-9 in particular is tantamount to the dysfunction of the cell in cancer and multiple sclerosis in its "re-modeling gone mad" natural function akin to a rapist.
This article breakdown will discuss a skin disease and its treatment with photo-chemotherapy and the invasion of MMP-2. It appears that the MMP-2 serves in a regulatory type function to restore the normalcy to the melanocyte along with alpha MSH. This may explain the effect of the heat therapy efficacy in Metastatic Pancreatic Cancer .

As in renal cells "representing " all cells with respect to their pathologies (MMP-9 dysfunction of overactivity) the skin also may give a hint as to how to put the MMP-9 back in check. My gut feeling is that the TNF-alpha recepetor must be blocked with monoclonal antibody as it is in septic shock to allow for therapy to be given and normalcy to return to the MMP-9 "digestion" run wild. I do realize that as a theorist of medical informatics I do not have the data except that henceforth given to us from previous studies. A review of the arginine, citulline biochemistry will also inevitably profitable as well as that of inducible nitric acid synthase and HuR ELAV factors involved in the stabilization of mRNA of MMP-9

Source / Source 2002, vol. 15, no6, pp. 426-432 [7 page(s) (article)] Editeur / PublisherBlackwell, Oxford, ROYAUME-UNI (1987-2007) (Revue)Localisation / LocationINIST-CNRS, Cote INIST : 21408, 35400010678572.0030

It is known that the migration of melanocyte precursors (melanoblasts) from the outer root sheath of hair follicles into clinically depigmented epidermis is crucial to the repigmentation of vitiliginous skin treated with photochemotherapy (PUVA), but such migratory cells must penetrate extracellular matrix tissue barriers in vivo. To test the hypothesis that matrix metalloproteinases (MMPs) are required for this process, we determined whether cultured melb-a cells, an immortal line of melanoblasts isolated from neonatal mouse epidermis, express and secrete MMPs and whether a synthetic metalloproteinase inhibitor, GM6001 (Galardin), inhibits their migratory behavior in vitro. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine the patterns of MMP expression by melanoblasts at the mRNA and protein levels, respectively. The proteolytic activities of MMPs secreted into the culture medium were assessed by gelatin zymography. The capacity of melanoblasts to migrate on fibronectin, laminin or laminin-5 substrates was estimated using Transwell migration assays. The results show that MMP2, MMP9 and MT1-MMP transcripts are expressed by these melanoblasts, but only MMP2 is secreted and activated in the extracellular environment. Although the therapeutic efficacy of PUVA in stimulating repigmentation of vitiliginous skin might derive from direct effects of UVA and/or 8-methoxypsoralen (8MOP), recent studies have shown that keratinocyte-derived factors induced by ultraviolet radiation, especially α-melanocyte stimulating hormone (aMSH), play a major role in regulating melanocyte function. Therefore, we also examined whether 8MOP and/or aMSH are involved in the up-regulation of MMP2 expression in melanoblasts. Western blotting and zymographic analyses revealed that MMP2 synthesis and secretion were induced by 8MOP and/or by aMSH. This induction of MMP2 resulted in significant increases of migration by melanoblasts on laminin or on laminin-5 substrates, while concomitant treatment with GM6001 blocked that induced migration. Taken together, these results suggest the importance of MMP2 in melanoblast migration