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Cell: Key cell that stops cancer from metastasising found

Time:2024-10-10 08:02:38     Views:311

International Business Department           Liu Bojia           October 10, 2024

  Cancer metastasis is an extremely dangerous event for cancer patients; when some cancer cells are dislodged from the in situ tumour into the circulatory system, they can regrow in any organ. Since the development and progression of metastatic tumours are often unpredictable and it is difficult for doctors to intervene in this regard, cancer metastases are also an important cause of death for cancer patients.

 

  Chronologically, disseminated cancer cells (DCC) shed from a tumour in situ spread long before the symptoms of metastasis appear. However, the process by which different DCCs grow into new tumours is not uniform, with some DCCs being more aggressive and others remaining dormant for long periods of time. Scientists are trying to figure out which mechanisms keep DCC in a dormant state, so that by enhancing such mechanisms, they can hopefully prevent or even stop metastasis from occurring.

 

  A key clue was found in a new study in the journal Cell on 7 October, in which the authors found that macrophages residing in organ tissues are key to directing DCC dormancy. When free DCC enters a new site, specific macrophages respond, activate immune signals, and regulate cancer cell signalling pathways by secreting TGF-β2 proteins, forcing the cancer cells to stop proliferating and enter a dormant state.

 

  For the study, a team of researchers from the Albert Einstein College of Medicine and the Icahn School of Medicine at Mount Sinai constructed a group of model mice for metastatic breast cancer, in which the breast cancer cells are highly susceptible to metastasis, with the lungs being the most common site of metastasis. The authors analysed mice with tumours at different stages and showed that in the early stages when DCC enters the lungs and forms aggregates, the number of alveolar macrophages (AM) in the lungs increases and dominates the macrophage population.

 

  These macrophages living in the lungs were originally responsible for regulating lung tissue homeostasis, lung development and performing immune surveillance functions. The authors found that when DCC entered the lungs, alveolar macrophages also became active and interacted with cancer cells in the alveolar lumen. The proximity of alveolar macrophages to DCC caused the DCC to change from an ellipsoidal shape to an ‘M’ shape, although the interaction did not cause cell death. The authors found that alveolar macrophages achieve another way of controlling cancer cells - by triggering growth arrest.

 

  In a follow-up experiment, the authors co-cultured some DCC precursor cells (EL cells) and alveolar macrophages in the same environment, and the results were similar to the phenomenon observed in the mouse samples, where the EL cells also gradually transformed into the M-type. In addition to this, the authors found a complete cessation of EL cell growth and a significant reduction in the ability of the cells to form clones. This process occurs when TGF-β2 expressed by alveolar macrophages binds to the cancer cell's receptor, which continues to stimulate the signalling pathway to keep the cancer cells in a dormant state.

 

  However, in the case of late-developing cancer cells that come into contact with alveolar macrophages, cancer cell growth is not inhibited, suggesting that dormancy control by alveolar macrophages is only useful for early cancer development. In contrast, the authors found that over time, DCC may gradually become resistant to this dormant signalling and regain invasiveness as well as achieve metastasis, which may also be one of the reasons why the time to metastasis varies between cancer patients.

 

  Study corresponding author Julio A. Aguirre-Ghiso, PhD, said, ‘Understanding the mechanisms by which immune cells control DCC promises to lead us to entirely new strategies for stopping cancer metastasis.’ He believes that enhancing the signalling of macrophages, such as alveolar macrophages, to keep DCC dormant for long periods of time may be a promising way to fight cancer.

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