Cancer and Blood Vessels: Recruiting Others or Becoming One Themselves?
Cancers that form in organs like the stomach and lungs are collectively called "solid tumors," to distinguish them from hematologic (blood) cancers. Normal cells turn cancerous due to genetic mutations and other factors, forming solid tumors. A characteristic of cancer is unlimited proliferation, where a single cancer cell multiplies rapidly. As a result, they form a mass, becoming a "solid tumor." In this state, the cancer cells in the center have reduced access to oxygen and become "suffocated." The main protein that senses this suffocating (low-oxygen) state is called HIF. In suffocated cancer cells, HIF produces other proteins, such as VEGF and PDGF, and releases them outside the cell. Outside the cell, these proteins like VEGF signal to nearby blood vessels, essentially saying, "Come over here." As a result, blood vessels branch out toward the cancer cells, allowing them to secure not only oxygen but also nutrients and a route for metastasis. This phenomenon, where new blood vessels branch from existing ones to form a vascular network, is called angiogenesis, and it is known to be involved in diseases such as cancer. Drug development aimed at inhibiting angiogenesis to "starve" cancer cells (by cutting off their supply of oxygen and other nutrients) is being conducted worldwide.
Meanwhile, our laboratory is conducting somewhat unusual research. In the angiogenesis described above, blood vessels are primarily formed from vascular endothelial cells. However, we are considering the possibility that cancer cells themselves can transform into blood vessels. This phenomenon, where cancer cells themselves mimic blood vessels, is called "vasculogenic mimicry." Figure 1 shows a photograph of cancer cells undergoing vasculogenic mimicry. You can see that they are forming a network, much like blood vessels. Depending on the cell type, this can be observed in less than half a day after treating the cells. While angiogenesis is initiated by the "oxygen deprivation" signal and the proteins involved are fairly well understood, vasculogenic mimicry is a biological phenomenon with many unknowns. Our laboratory is tackling this challenge using genome editing technology, which has become prevalent in recent years. Although we started researching vasculogenic mimicry relatively recently, we have already discovered important proteins and have been able to publish two peer-reviewed papers. Both were supported by the university's committee for subsidizing international academic publication fees and are open access, so please take a look.
Figure 2 is my blood donor card. I (really) dislike injections because they are painful, but I occasionally donate blood out of a sense of duty, both because I want to help people and because I research blood vessels. I sometimes run into unexpected people at the blood donation center. Recently, I happened to be there at the same time as someone who works at the co-op on the Yagami Campus. Perhaps things related to blood vessels have a way of connecting various things and people (though there is no scientific basis for this).
The concept of "starving" cancer cells is very appealing from the perspective of cancer treatment, especially chemotherapy. It is not yet clear which strategy cancer cells preferentially use—"recruiting others" (angiogenesis) or "becoming one themselves" (vasculogenic mimicry), as mentioned in the title. However, while focusing on basic research, our team of highly capable students and staff is united in our daily efforts to conduct research that will be useful.