What are you aiming to achieve?

Fig. 1 Vascularization towards the black tumorous mass on the right
(From “The biology of Cancer” by Weinberg RA )

If you joined all the blood vessels that run throughout your body end-to-end they would encircle the earth 2.5 times. Blood vessels are the lifeline of an organism and are also distributed throughout a range of lesions, so that they play an extremely important role in the onset and progression of a disease. Circulatory disorders and vascularization are closely related both to the progression of conditions and to their treatment in the most common causes of death among Japanese people (cancers, cardiac disease, and cerebrovascular disease). Specifically, when treating cancer, which kills around 300,000 people per year in Japan, while the methods most often used involve directly attacking the tumor cells, the drugs used to do so have side-effects that impact the cells that create hair, as well as our reproductive organs, bone marrow, etc. At the same time, cancer gathers blood vessels in order to grow and metastasize, and is known to cause the formation of many new blood vessels (Fig. 1).

Fig. 2 Development of a drug that operates only on cancer blood vessels

Researchers focusing on this have now developed new anti-cancer drugs known as anti-angiogenic inhibitors. These attack not the cancer cells themselves, but rather the blood vessels that are gathered around the cancer cells used to deliver nutrition and oxygen, thereby tactically attacking the cancer. At present, these are garnering a lot of attention as a relatively successful new type of anti-cancer drug. We now know, however, that they also have side effects, including hypertension, and it is thought that this may be due to the fact that they work not only on the tumor blood vessels, but on normal blood vessels as well. In other words, in explanation of the diagram below, current drugs work on tumor blood vessels, but also affect normal blood cells (the yellow circles in Fig. 2). We have succeeded in isolating the cells of tumor blood endothelial cells and successfully cultivating them, allowing us to discover specificity markers only belonging to cancerous blood vessels. New drugs are expected to target only these abnormal markers (the pink square in Fig. 2), and have no effect on regular blood vessels, only being effective in regard to the cancer blood vessels, with no side effects, allowing more effective attacks on the blood vessels that nurture cancer. We are working to develop drugs that only work on this sort of tumor blood vessel.

What sort of equipment do you use to do what type of experiments?

We need to be able to isolate only vascular cells (endothelial cells) from cancer tissues. We use fluorescently labeled antibodies in regard to cell surface molecules occurring in the vascular endothelium to cause a reaction (Fig. 3), after which we use a technique known as flow cytometry to isolate the cells. The use of flow cytometry causes the cells to flow through liquid, making it possible to isolate only those that are fluorescently labeled using a laser beam (Fig. 4). The device looks like the one in Photo 1. The vascular endothelial cells obtained in this way are cultured and used in the development of new drugs.

 

 

What are you aiming for next?

While there are many anti-cancer drugs currently under development, unfortunately, there are still no drugs in existence that can be used against a wide range of cancers without any side effects. I would like to develop an anti-cancer drug that can be used to target tumor blood vessels that are incorporated in cancer and nurture it so that it can be used on a common target in a wide range of cancers, with no side effects on regular blood vessels. I would like to contribute to the dawn of an age in which we can cure cancer, in the same way as the development of antibiotics has gone on to save many people’s lives by preventing infection.

 

References

1. *Hida K., Maishi N., Torii C., Hida Y.：Tumor Angiogenesis—Characteristics of Tumor Endothelial Cells, Int J Clin Oncol, in press
2. *Hida K., Maishi N., Sakurai Y., Hida Y., Harashima H.：Heterogeneity of tumor endothelial cells and drug delivery, Adv Drug Deliv Rev, in press
3. *Hida K., Ohga N., Akiyama K., Maishi N., Hida Y.：Heterogeneity of tumor endothelial cells, Cancer Sci, 104(11), 1391-1395, 2013
4. Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and *Hida K.：CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property, Int J Cancer, 137(12), 2825-2836 2015
5. Osawa T., Ohga N., Akiyama K., Hida Y., Kitayama K., Kawamoto T., Yamamoto K., Maishi N., Kondoh M., Onodera Y., Fujie M., Nonomura K., Shindoh M. and *Hida K.. : Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis, Br J Cancer, 109(8), 2237-2247, 2013