Enzyme behind cancer spread found

Hi all.

This is a JMHO post. Just food for thought, nothing more, in response to this thread.

LOX (lysyl oxidase), as suggested in the link, may be an aider of breast cancer metastasisthrough complicated connective tissue interactions. LOX may make a metastatic site fertile ground for the cell to settle and grow through its messenger proteins which prepare the site.

Matrix Metalloproteins (MMP's) are intricately involved with collagen and collagen breakdown in our body. I discovered this when reading about joints, as mine hurt so much on the AI's. I also discovered Femera for ER+ bc is a potent inhibitor of MMP's. I wrote about it in a past post:

"I have read that Femara can influence collagen proteins, and act on the MMPI family of proteins (matrix metalloproteinase inhibitors) which are important in collagen maintenance. Collagen is present in our bones and joints, and tendons. Collagen, as I understand it from my DH, does not divide or produce more due to the absence of nuclei within a collagen cell..."

So cp418 and ladies, one potential LOX inhibitor may be possibly Femara. Maybe this is one contributing factor to the decrease distant mets observed with Femera, which was one finding suggested in the MA-17 trial. Perhaps all AI's, if similarly studied, would be found to be MMP inhibitors. I just don't know. Here is an abstract reviewing findings of Femera and MMPI (inhibitor of MMP):

P450 aromatase catalyzes the conversion of androgens to estrogens and plays a key role in the cell growth of hormone-dependent breast cancer in postmenopausal women. On the other hand, matrix metalloproteinases (MMPs), which can degrade almost all components of the extracellular matrix, play a crucial role in tumor cell invasion and cancer metastasis. In the present study the effect of letrozole on cell proliferation of estrogen receptor (ER)-positive MCF-7 human epithelial breast cancer and MCF-12A human mammary epithelial cells was studied. The effect of letrozole on the in vitro release of MMPs, particularly type IV collagenases (MMP-2 and MMP-9), by the ER-positive MCF-7 cells was also investigated, using a solid-phase method of high sensitivity and accuracy. Using RNA isolates from cell lines MCF-7 and MCF-12A, reverse transcriptase-polymerase chain reaction analysis revealed that only MCF-7 cells express the P450 aromatase gene. Study of the effects of letrozole alone and the hormones 17-beta-estradiol, testosterone and 4-androstene-3, 17-dione in the presence and absence of letrozole on cell growth at the DNA synthesis level showed that letrozole significantly suppressed the endogenous aromatase-induced proliferation of MCF-7 cells. The majority of MMPs secreted by MCF-7 cells were identified in their pro-forms, which was in accordance with the low metastatic potential determined for these cells. After treatment of cells with letrozole (10 nM) for 24 and 48 h, significant inhibition of MMP levels was obtained. Furthermore, concurrent treatment of MCF-7 cells with 17-beta-estradiol in the presence of letrozole significantly suppressed the estradiol-induced stimulation of MMP levels. The data obtained suggest that letrozole is a potent in vitro inhibitor of cell proliferation and of type IV collagenases expressed by ER-positive MCF-7 cells and may be of value for suppressing breast tumor growth and invasiveness. Copyright 2003 Wiley-Liss, Inc."

Several years ago, here on a breastcancer.org expert presentation on breast cancer metastasis, I heard the expert asked if he had any recommendation on OTC supplements if any to take. He stri limited his response to Vitamin D but not a multivitamin. I have pondered that for many years, being aware that a multivitamin typically contains what are called "trace minerals" like iron, zinc, copper, cadmium, selinium etc...I was aware that cadmium is not felt wise to take with a history of cancer. But still I wondered if there was more to this statement evolving from a research angle. Today perhaps, through cp418's link, the "more" might be suggested. Copper, it turns out, may be involved with the activation of lysyl oxidase (LOX), which through it's enzyme action, may contribute to messenger proteins around the body. Here is an article (not definitive proof, btw) talking about this:

Induction of Lysyl Oxidase with Copper

"Lysyl oxidase is a copper metalloenzyme found primarily in connective tissue (edit= collagen, elastin and fibronectin). The enzyme catalyzes (edit= facilitates or makes to occur)...in collagen and elastin preparatory to the formation of... cross links in these proteins" (Sorry, I left out all the chemical gooblelygook)   http://www.jbc.org/cgi/reprint/254/3/621.pdf 

Well, my point is that perhaps we may today be able to fight distant metastasis. If you are ER+, you might consider taking an AI such as Femara after Tamoxifen or as a starter hormonal if you can tolerate it. And if you can find a multivitamin without the trace minerals, that might be good to do so as to just get what you already take in through one's diet. 

These are just my thoughts, with some articles posted to show how I connect my thoughts. For clarification, I do take Femara (switched from Arimidex at 5 years) and I do not take a multivitamin. Just Vitimin D, and that's a story unto itself worthy of a different post and time.

My best to you all, and as usual cp418, thanks for getting us thinking.

Tender 

Thanks for the discussion, Tender. It is very significant if letrozole has this additional mechanism of action in addition to it's hormonal inhibition, and might prove to be an important tool in triple negative BC. I hope this turns out to be true, we need every intervention we can find for TNs.

Interesting about the copper, Tender. We have well water and I have read that most wells in our area have higher levels of copper.......hmmmmmmmmm

http://www.newsobserver.com/2012/10/28/2433333/unc-team-targets-cancer-helper.html