total regression of orthotopic (implanted) tumors with RNAi to uPARR, MMP9

[Lani]

Int J Cancer. 2007 Jul 26; [Epub ahead of print]
RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth.

Kunigal S, Lakka SS, Gondi CS, Estes N, Rao JS.
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL.
The serine protease urokinase-type plasminogen activator (uPA) plays a significant role in tumor cell invasion and metastasis when bound to its specific receptor, uPAR (also known as CD87). In addition to the uPA-uPAR system, matrix metalloproteinases (MMPs) are involved in tumor cell invasion and metastasis. In this study, we achieved specific inhibition of uPAR and MMP-9 using RNAi technology. We introduced small interfering RNA to downregulate the expression of uPAR and MMP-9 (pUM) in breast cancer cell lines (MDA MB 231 and ZR 75 1). In vitro angiogenesis studies indicated a decrease in the angiogenic potential of the treated cells; in particular, a remarkable decrease was observed in the cells treated with bicistronic construct (pUM) in comparision to the controls. Additionally, bicistronic construct inhibited the formation of capillary-like structures in in vivo models of angiogenesis. Similarly, the invasive potential and migration decreased dramatically when treated with the bicistronic construct as shown by matrigel invasion and migration assays. These results suggest a synergistic effect from the simultaneous downregulation of uPAR and MMP-9. We also assessed the levels of phosphorylated forms of MAPK, ERK and AKT signaling pathway molecules and found reduction in the levels of these molecules in cells treated with the bicistronic construct as compared to the control cells. Furthermore, targeting both uPAR and MMP-9 totally regressed orthotopic breast tumors in nude mice. In conclusion, our results provide evidence that the simultaneous downregulation of uPAR and MMP-9 using RNAi technology may provide an effective tool for breast cancer therapy. (c) 2007 Wiley-Liss, Inc.
PMID: 17657740 [PubMed - as supplied by publisher]

[R.B.]

http://www.ncc.go.jp/en/nccri/annrep....Chemothe.html


On my web wanders again!

This is for a different cancer and this is all there is - thought provoking none the less.

RB


Abstact

Inhibitory Effects of Oleic and Docosa-hexaenoic Acids on Lung Metastatic Colony Formation and Matrix Metalloproteinase (MMP) Activity

Oleic acid (OA) and docosahexaenoic acid (DHA) were found to significantly inhibit lung metastasis in a colon carcinoma-26 tumor cell metastasis assay system, the fatty acids being well absorbed into tumor tissues. Arachidonic acid and linoleic acid contents were markedly decreased by treatment with DHA. Gelatinolytic activity of the 57-kD (MMP-2) and 92-kD (MMP-9) isoforms of type-IV collagenase showed a clear reduction with OA and DHA, respectively. These results suggest that the effects of OA and DHA on metastasis might be due to inhibition of type-IV collagenase activity.(52-54)

[R.B.]

This I think is the trial report I have just found whilst looking for something else.

Again thought provoking. The addition of LA reduced efficacity of DHA, and surprisingly so did EPA although it worked on its own. More info required.

http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum