Myeloma and stress

December 13 2007 post: Other myeloma bloggers have posted about a recent study (abstract: http://tinyurl.com/2w4ndb) showing the link between myeloma and stress. My friend Sherlock sent me the full study, so I will try to provide some additional information. Conducted by a team of researchers at the Ohio State University Medical Center, this study was published in November 2007 in “Brain, Behavior and Immunity,” which by the way looks like a very interesting publication. I must keep my eye on it.

The study is titled “VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine.” A couple of notes before proceeding. Noradrenaline, also known as norepinephrine (NE), is a hormone and neurotransmitter involved in alertness and concentration, among other things. It is involved in heart rate, blood pressure and blood sugar level increases. VEGF stands for “vascular endothelial growth factor,” and is an evil signalling protein that is linked to tumour progression, feeding cancer cells, etc. Read this excerpt from an IMF article written in 2001 (http://tinyurl.com/2yh49k): “Dr. Kenneth Anderson of the Dana-Farber Cancer Center mentioned that VEGF might not only be important for the formation of new blood vessels in MM but also has the potential to stimulate directly the proliferation and migration of myeloma cells. His group demonstrated that production of VEGF by myeloma cells can be stimulated by activation of the CD40 molecule on the surface of the tumor cells.” CD40, we meet again!…remember my CD40 post? I am not done yet with natural ways we can use to inhibit CD40, I just need to find the time to read the studies that Sherlock sent to me.

But let’s get back to VEGF. The Ohio stress study tells us that “VEGF is a crucial cytokine that directs and promotes tumorogenesis and potentiation in the marrow. VEGF levels correlate with overall prognosis and associated bone destruction, which contributes substantially to clinical morbidity.” I told you VEGF was evil! In fact, I suggest that from now on it be known, perhaps more appropriately!, as “Very Evil Growth Factor.”

The introduction begins: “There is evidence that psychological factors can affect the incidence and progression of some cancers.” And, in fact, there is definitely a connection between our IL-6 levels and chronic stress, which is actually a topic on my infinitely long to-be-researched list. That is one reason why I was most interested in the finding, reported in the Ohio study, that NE has been found to stimulate IL-6 and IL-8 in human melanoma cells. But these two cytokines are also actively involved in myeloma. We know all about evil IL-6, but IL-8 has also been connected to progression in myeloma. No comment necessary, methinks.

Discussing a previous study, the Ohio researchers report that stress can inhibit T cells from responding “to tumor-associated antigens on tumor cells of immunogenic tumors.” T cells, hmmm, that sounds familiar.. And the effects caused by stress may “may contribute to tumor progression independent of its effects on the immune system.” Well, we knew that stress is bad for us, but this goes a bit beyond “bad.”The researchers tested three myeloma cell lines in different stages of development. All three had “the potential to respond to NE,” but one in particular “exhibited the greatest NE-dependent response.” Interestingly, this cell line came from someone whose myeloma was aggressive but ”in the earliest (and comparatively longest) clinical phase—i.e., where disease is confined to the bone marrow.” This could mean that in early stages perhaps the blood supply to the malignant cells could be diminished simply by inhibiting NE, which would not kill the malignant cells, of course, but should theoretically slow down tumour growth and disease progression.

Toward the end of the study, we find the following: “Whether the stress-associated activation of the sympathetic nervous system results in the upregulation of NE levels in the bone marrow is unknown. However, observations described here suggest the potential for a stress-associated stimulation of proangiogenic properties of MM cells through the upregulation of NE levels.” The Ohio team adds that “the mechanism involved in the NE-dependent increase in VEGF release by MM cells is not known.”So let’s have more studies like these instead of inanities of the following sort (I glanced at this article this morning and could hardly believe my eyes): “new research suggests that the presence of other people may enhance our movie-watching experiences. Over the course of the film, movie-watchers influence one another and gradually synchronize their emotional responses” (http://tinyurl.com/299s5x). Ehhhh??? You’ve got to be kidding. Isn’t it common knowledge that if you go see a fantastic movie with someone you don’t like, most likely you will hate it, but if you go to see the same movie on your own or with a good friend, you will probably love it, blablabla? Do we really need actual STUDIES to look into this sort of twaddle? Come on!

I would like to finish by saying that I hope to have time at some point to look at the other NE-cancer studies. And then there is the whole related issue of beta-blockers, which the Ohio team suggests might be beneficial for myeloma patients (but more info is needed, they add). Anyway, that topic too complicated to get into today. Interesting, though.

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