Scientists Can Stop Bladder Cancer To Metastasize To Lungs

Scientists Can Stop Bladder Cancer To Metastasize To Lungs

According to new study conducted at the University of Colorado and published today in the Journal of Clinical Investigation, researchers were able to demonstrate the way in which bladder cancer metastasizes to the lungs and to develop a method that can stop bladder cancer dissemination into the lungs. This study is very important because patients with localized forms of bladder cancer present an 80 percent five-year survival rate, unlike patients with metastasizing forms of bladder cancer who present 20 percent survival rate at three years.

With this study scientists demonstrated that a protein that is involved in cancer cell migration, called versican is responsible for lung metastasis and high levels of this protein are associated with aggressive forms of bladder cancer and with poor prognosis. Researchers also observed that cancer cells synthesize a protein called RhoGDI2 which blocks the production of versican, thus stopping the migration of cancerous cells into the lungs and the capacity of bladder cancer to produce lung metastasis.

“For a decade, we’ve known that the major challenge of treating bladder cancer is treating or preventing the metastatic form of the disease. This study represents an advance in the latter “ by preventing the spread of bladder cancer to the lungs, we could improve patient survival,” says Dan Theodorescu, MD, PhD, the study’s senior author.

In their process of metastasis, cancer cells dose not become suddenly mobile and start to float through bloodstream or lymphatic flow to other organs. Instead, it was observed that cancer cells present the capacity to float through bloodstream for a long period of time and to metastasize only when are able to grow in an organ where this cells are attached, in this case the lungs.

Cancer Cells

When cancerous cells are attaching to an organ and start to metastasize they are distressed and become weaker. Cancer cells distress is expressed by the secretion of versican, a protein which has the ability to attract macrophages, cells that are part of the body’s immune system and participate to the immune response.  Process by which macrophages are attracted by cancer cells into organs presents both advantages and disadvantages. Advantages are represented by the fact that macrophages are immune system cells which have the ability to destroy cancer cells by phagocytosis. The big disadvantage is that in their process of helping healthy cells to survive, macrophages also promote the development of cancerous cells that reached other organs, thus promoting metastasis of cancer.

In conclusion, the more versican is secreted by cancer cells , a greater number macrophages are attracted, which in addition to their protective effects on healthy cells, enhance the growth of cancerous cells and the appearance of metastasis, in this case in the lungs.

But scientists observed that a protein secreted by cancer cells called RhoGDI2 can reduce the secretion of versican, because in organs were cancer cells secrete more RhoGDI2 the levels of versican are lower and the number of macrophages is lower, which make cancer cells to become sensitive and to be destroyed by the immune system. When researchers added RhoGDI2 to metastatic tumor, the level of versican became lower and metastases began to shrink.

“We believe this study provides an important contribution to the scientific literature by delineating for the first time a new mechanism of metastasis suppression, namely that suppression of metastasis is possible by altering the tumor microenvironment, including reducing the presence macrophages,” Dan Theodorescu added.

This study shows an other important step in cancer research because it was demonstrated that versican can attract macrophages only by the secretion of some proteins called CCL2, for which were discovered drugs that inhibit their activity, drugs that are now tested in clinical trials for other diseases.

Scientists hope that in the future CCL2 inhibitors to become a part of bladder cancer treatment scheme, especially for bladder cancer that express increased levels of versican and decrease levels of RhoGDI2. By inhibiting CCL2 proteins, the capacity of versican to attract macrophages can be reduced, thus can be stopped metastasis development, fact that improve the outcome of patients with aggressive forms of bladder cancer.