Monday, July 02, 2007

Finding protection from tumor growth in unexpected places

As just about anyone who takes even the simplest medications knows, almost everything has side-effects. Generally, there's no free lunch. The aspirin that reduces your fever and (maybe) makes your hangover a little less painful can also cause ulcers and stomach bleeding.

Among the many thousands of proteins, hormones, enzymes, and the like that are active naturally in your body at any one time, most presumably are there for a beneficial purpose. But not always. Some have a distinct Jekyll/Hyde quality about them.

Consider, in particular, the hormone known as angiotensin II. It is part of what is called the renin-angiotensin system, which helps regulate blood pressure. Overlooking a number of details, one of the key functions of angiotensin II is to quickly constrict blood vessels, to minimize blood loss in the event of serious injury. However, because it raises blood pressure, the body needs for it not to be around most of the time, to avoid dangerous hypertension.

The way the body handles this is by producing a slightly different hormone instead, angiotensin I, which can be quickly converted, when required, into angiotensin II by means of an enzyme called simply angiotensin-converting enzyme (ACE). It's ACE we're really here to talk about in this note, because it appears to have several other functions besides the one it's named for. Ironically, one of the strategies for treating hypertension is to inhibit ACE, because of the need to keep blood pressure under control. Yet some of its side effects, unrelated to blood pressure, seem beneficial.

Finding Protection From Tumor Growth In Unexpected Places
Researchers have discovered that an enzyme commonly involved in regulating blood pressure also provides protection from tumor growth when strongly expressed in immune cells.

ACE, in fact, is involved in a surprising number of other processes in addition to restraining tumor gowth via its immune system activity.
Angiotensin-converting enzyme (ACE) plays a direct role in controlling blood pressure and is a common therapeutic target in hypertension. However, it also plays roles in such diverse processes as fertility, immune cell development, and atherosclerosis, and a few studies have even suggested a role for ACE in generating an effective immune response.

The researchers used experimental mice (ACE 10/10 mice) that express ACE only in their macrophages. The findings were quite intriguing.
When injected with aggressive melanoma cells, normal mice developed large melanoma tumors whereas ACE 10/10 mice developed only very small tumors. The resistance of ACE 10/10 mice to melanoma growth was confirmed using several different melanoma cell lines and by using different strains of mice expressing high levels of ACE in macrophages. Interestingly, the small tumors of ACE 10/10 mice contained significantly higher numbers of white blood cells, suggesting a large anti-tumor immune response.

To confirm the existence of an ACE-specific anti-tumor immune response, normal mice were depleted of their bone marrow and transplanted with ACE 10/10 bone marrow. When the transplanted normal mice were then injected with melanoma cells, they too were able to control tumor growth. The immune response involved not just the ACE-expressing macrophages but also increased numbers of cytotoxic T cells and levels of immune-activating chemicals and decreased levels of immune-suppressing chemicals. Finally, the ACE 10/10 macrophages alone could direct the immune response and convey protection as direct injection of these cells into melanoma tumors of normal mice yielded decreased tumor size.

It will be very interesting to learn what further research reveals about how ACE enhances the immune system.

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