Not long ago, while reminiscing with my friends about some of the trends from our adolescence, one of my favorite books from that time came to mind: “The Fault in Our Stars,” by John Green, a bestseller that even had a movie adaptation. In it, the protagonist is Hazel Grace Lancaster, a teenager living with thyroid cancer that has spread to her lungs. She meets Augustus Waters in a support group for young people with cancer, and they both experience a beautiful yet tragic love story.
Years later, while analyzing Hazel's particular case from a different perspective, perhaps as a scientist and not as the teenager who cried a lot over the novel's ending, there is one detail that has very little to do with the plot that caught my attention: why, if Hazel's cancer was originally in her thyroid, did it ultimately affect her lungs to the point where she needed to carry an oxygen tank everywhere? Why do the cells of certain tumors seem to have a “preference” for specific organs when forming metastasis?
Metastasis is the process by which cancer cells spread from the primary tumor to distant sites in the organism, where they manage to establish themselves and proliferate. Very simplistically, for this to happen, the cells must leave the original tumor, access the bloodstream or lymphatic circulation, survive the immune response, and exit the vessels to settle in the new tissues. However, reaching an organ does not guarantee that they can colonize it.
In fact, it has been observed that the distribution of metastasis is not random; rather, different types of cancer present their own “preference” sites, a phenomenon known as “metastatic organotropism.” For example, prostate cancer has a strong tendency to metastasize in the bone; uveal melanoma (a type of eye cancer) tends to colonize the liver, and differentiated thyroid cancer can spread to the lungs, as in the case of Hazel Grace.
But what does this preference depend on? Part of the answer lies in the interaction between tumor cells and the microenvironment of the receiving organ. Since the cells of the same tumor often vary greatly from one another, some may have characteristics that allow them to exploit signals and specific factors from certain organs. In turn, each tissue presents particular conditions (such as the availability of nutrients or certain molecules) that can favor or hinder the survival and expansion of tumor cells. Even the primary tumor can release signals that modify distant organs long before the cancer cells arrive, contributing to the formation of what is known as the “premetastatic niche.”
There are also adaptation strategies that are even more specific and fascinating. In certain types of tumors, such as those of the breast and prostate, some cells may express molecules characteristic of bone cells, allowing them to “mimic” the bone environment, adapt better to it, and eventually colonize and proliferate.
Metastasis is one of the most complex aspects of cancer biology, and as we saw in the article, its patterns of dissemination do not seem to respond to a single cause, but rather to a set of diverse factors. Perhaps that's why John Green decided to become a writer, focusing on the romance between Hazel and Gus and leaving the intricate and tedious details to the boring nerds, that is, the scientists.
By Manuela Beltrán, a student in the Biotechnology degree program at UADE.
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