Cancer's fearsome travelers
So how do those circulating tumor cells find the best soil in which to pitch their tent? Researchers from Paget on have noted that certain cancer cells prefer certain organs. Breast cancer cells, for instance, often spread to bone, brain, and liver, while ovarian cancer cells almost never lodge in the lungs. No one knows for sure why this is the case, but research now suggests that it has to do with signaling between the invading cells and the host. A research team at M. D. Anderson has identified what it calls "ZIP codes" on blood vessel walls that may help cellular explorers find a hospitable home. Says M. D. Anderson's Wadih Arap: "Cells in the blood vessels aren't generic. Cancer may be using the vasculature as beacons." If this theory is borne out, ZIP codes might someday offer the hope of delivering drugs in a very targeted way.
Once a wandering cancer cell finds the right address, it still has to infiltrate the organ itself. The thought is that different cancers carry different sets of keys, and they can gain entry only if there's a matching lock. That helps explain why some cancers pass harmlessly through the lungs without lodging there. In 2001, researchers showed that the preferred lodgings of breast cancer and melanoma were basically "advertising" themselves with chemicals called chemokines. Guest and host, in other words, were on the same wavelength. And once they find each other, the deadly dance begins. Breast cancer cells, for example, stimulate cells that break down bone. The more the bone breaks down, the more the cancer can grow.
So get them on the wrong wavelength; mangle their communication. That's in fact what drugmakers have in mind. Drugs capable of doing that might have to be taken indefinitely, since tumors can lurk undetected in the body for years. Research has even shown that tumor cells can mimic other kinds of cells by taking cues from their environment. Indeed, there is much to be learned about how the tumor's soil influences the progression of metastasis, and few of these discoveries are yet ready to translate to treatment. Thinking of the body as an unwitting but active participant in the process raises the intriguing question: Could our own chemical signals someday be used to block metastasis? After years of trying to crack the seed, many cancer researchers are now sifting through the soil in search of the answer.
Cancer's Itinerary
All metastasizing cells have the same basic plan, though for reasons not known some are picky about where they travel and set up camp. For example, the cells that break off from a primary breast cancer tumor often migrate to the brain.
1 The primary tumor taps into the local blood supply and thrives in the breast tissue.
2 Thousands of cancer cells routinely break off from the tumor and begin traveling through the body's blood and lymph systems. Most of these traveling cells perish, but some arrive in far reaches of the body, where they lodge in a blood vessel wall.
3 Once fortified, the cancer cells vacate the blood vessel and invade healthy organs.
[drawing labels] Tumor, Vessel, Cancer cells, Lymph nodes, Blood vessels
Rod Little--USN&WR
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