Discovery Could Lead to Ways for Decreasing Metastatic Disease

July 18, 2017
Kevin Hattori

In an article published in the journal Cell Reports, an international research team presents their discovery of a central mechanism that accelerates the development of metastases after surgery for the removal of cancerous tumors in the abdominal area. This study provides a possible treatment modality for cancer patients that can decrease incidence of deadly metastatic disease.

Surgical site in the peritoneal membrane of a mouse. The red mark shows the expression of LOX; The green mark shows the hypoxia (lack of oxygen) in the cells.

The study was conducted by Prof. Yuval Shaked and Prof. Peleg Hasson of the Technion-Israel Institute of Technology Faculty of Medicine, together with researchers from the Weizmann Institute, Italy and Finland. Prof. Shaked is also on the faculty of the Technion Integrated Cancer Center (TICC).

Tumor removal surgery is one of the most common ways to treat cancerous tumors, and more than 50% of all cancer patients undergo surgery. The purpose of the surgery is to remove all the cancerous tissues as well as the “margins” from the healthy tissue in order to prevent the recurrence of the tumor.

However, in many cases, the tumor redevelops from individual cancer cells remaining in the surgical site. The re-emergence is more violent than the primary tumor and is manifested in cancerous metastases – the development of cancer cells elsewhere in the body. Unlike primary tumors, which are relatively easy to treat with surgery and radiotherapy, metastases are a far more complex challenge and are responsible for about 90% of cancer deaths.

Prof. Peleg Hasson, of the Technion Rappaport Faculty of Medicine

The development of metastases after surgery is a well-known phenomenon explained by the fact that in reaction to surgery, which is a type of injury, the body develops an inflammation in the surgical site in order to protect it from infection. This inflammation leads, among other things, to a recurrence of cancer.

In the present study, the researchers found that tumor removal surgery in the abdominal area causes changes in the lung tissue that increase the likelihood of metastasis. These changes, mainly in the connective tissue of the lung, improve the ability of cancer cells to adhere to this tissue, and thus to develop new metastases. The researchers also found that the structural changes in the connective tissue are associated with an enzyme called lysyl oxidase (LOX). This enzyme, which is responsible for connecting the collagen fibers that are the main component of the connective tissue, changes the connective tissue structure and thus makes it easier for cancer cells to adhere to it. When the researchers inhibited the activity of this enzyme, a significant reduction in the ability of cancer cells to adhere to the lung tissue was achieved, resulting in the reduction of cancer metastases.

Prof. Yuval Shaked, of the Technion Integrated Cancer Center and Technion Rappaport Faculty of Medicine

After experiments on mice, the researchers examined the process in patients who underwent various abdominal surgeries, and found an increase in the levels of the enzyme in the human body as well, resulting in an increase in the number of metastases. They hope that the present study will lead to the development of LOX inhibitors in the future, which will prevent a recurrence of cancer in patients undergoing tumor removal surgery.

The study was supported by an ERC grant from the European Union and by the Rappaport Institute at the Technion.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

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