Detection of changes in lung tissue, indicating possible development of cancerous metastases, will allow diagnosis and preventive treatment
A new study from Tel Aviv University has revealed changes in healthy lung tissue, which are a preliminary sign of the possible development of cancer cell metastases. The changes were detected in an area known as the ‘microenvironment’ of the tumor, and found in connective tissue cells called fibroblasts. According to the researchers, understanding the metastatic process and diagnosing it at such an early stage may lead to life-saving preventive treatment.
Decipher the ‘black box’ of breast cancer
The study was led by Prof. Neta Erez, Head of the Department of Pathology at the Sackler Faculty of Medicine , along with a team of researchers in her laboratory, Dr. Ofir Shani and Dr. Yael Raz, as well as other researchers from Tel Aviv University, Tel Aviv Medical Center (Ichilov) , From the Sheba Medical Center and the Weizmann Institute The article was published in the journal eLife .
According to the researchers, in many cancers, including breast cancer, patients do not necessarily die from the primary tumor. The deadly cause, in the end, is the metastases, which reach vital organs and thrive there. Even in a patient who has undergone all the proposed treatments, including surgery to remove the primary tumor, followed by chemotherapy treatments and radiation designed to eliminate its remnants, metastases may appear several years later. In the follow-up methods used today, the metastases are detected when the disease is in an advanced stage, and medicine has no effective solutions.
For this reason, Prof. Erez’s group is researching the ‘black box’ – the same period of time between the apparent recovery and the appearance of the metastases, in order to understand the metastatic process and identify it already in the initial stages. The group’s research in recent years has shown that the target tissues in the organs to which the metastases are destined to reach ‘prepare the area’ for their absorption, and create a ‘friendly environment’ for them long before the metastases themselves appear. In the present study, the team looked for signs of these changes, which may be used in the future to identify the process at an early stage. They focused on connective tissue cells (fiber cells), called fibroblasts and found in, among other things, health.
What happens in the microenvironment of the metastases?
“In normal condition, fibroblasts play a key role in healing wounds and tissue damage, but recent studies have shown that cancer manages to recruit them and cause them to produce a supportive environment for it,” explains Prof. Erez.
The researchers performed sequencing of all expressed genes (transcriptomic sequencing) in fibroblast cells taken from the lungs of mice in a breast cancer model. They compared the results of the flooring in cells sampled from healthy lungs, lungs with micro-metastases (tiny metastases that cannot be detected by conventional clinical trials), and lungs with large metastases, in a state of advanced disease. Based on the changes identified from stage to stage, the researchers were able to characterize for the first time the process that takes place in the microenvironment of the cancer metastases, already in the early stages of preparing the surface for their absorption.
In addition, they specifically identified the proteins that drive the ‘rewiring’ processes in fibroblasts, and found that one of the key proteins in the process is Myc , which is known as a driving factor in accelerating the division of cancer cells. It now turns out that this protein also plays an important role in the change that occurs in fibroblasts towards the absorption of metastases.
“We have been able to characterize processes that occur in seemingly healthy tissues in preparation for the absorption of cancerous metastases. We believe that in the future our findings could help identify the metastatic process before the metastases themselves reach and take root in the target organ. Of millions of people all over the world, “concludes Prof. Erez.
Featured image: Prof. Neta Erez © Tel Aviv University
Reference: Ophir Shani et al, Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity, eLife (2021). DOI: 10.7554/eLife.60745
Provided by Tel Aviv University