In a new study from Tel Aviv University published in the journal Nature Cancer, researchers identified and characterized a new mechanism that facilitates the formation of brain metastases of breast cancer tumors and found that impairing this mechanism significantly reduced the development of brain metastases in mice. In the study, the researchers used models of melanoma and breast cancer brain metastases in an effort to reveal the mechanism by which neuroinflammation is activated in the metastatic niche in the brain.
The findings are relevant to patients with brain metastatic disease: High levels of the factor in patient blood could predict metastatic recurrence in the brain and a worse prognosis.
This marks yet another breakthrough made by Israeli scientists in the fight against cancer. In January, scientists from Israel’s Bar Ilan University found that a combination of cellular biology and structural biology advances the fight against breast cancer in a way “never before possible.”
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And Israeli startups like MICA AI Medical are developing new treatments for cancer as well as ways to detect the disease at much earlier stages.
As for the new study, the researchers explained that brain metastases are one of the deadliest forms of cancer metastasis. They are 2-10 times more common than tumors of the central nervous system (CNS). Despite the progress achieved in recent years in development of novel treatments for melanoma and breast cancer, brain metastasis remain highly lethal with grave survival rates of less than one year in many cases. The incidence of brain metastases has been increasing in recent years, probably as a result of improvements in diagnostic methods as well as progress in the treatment of metastases in other organs. Therefore, developing better therapeutic strategies for brain metastasis is an urgent need.
The research was led by Prof. Neta Erez, head of the laboratory for the biology of tumors from the Department of Pathology at the Sackler Faculty of Medicine, and members of her team: Omer Adler, Yael Zeit, and Noam Cohen, in collaboration with Prof. Shlomit Yust Katz from Rabin Medical Center (Beilinson Hospital) and Prof. Tobias Pukrop from Regensburg Hospital, Germany. The study was supported by the Melanoma Research Alliance (MRA), the Cancer Biology Research Center at Tel Aviv University, the Personalized Medicine Program of the Israel Science Foundation (ISF IPMP) and the German Cancer Research Foundation (DFG).
In this new study from the Tel Aviv University, the researchers show that Lipocalin-2 (LCN2) is a key factor in inducing neuroinflammation in the brain. Moreover, the researchers found that high LCN2 levels in patients’ blood and brain metastases from several types of cancer are associated with disease progression and reduced survival. LCN2 is a secreted protein that functions in the innate immune system and was originally discovered due to its ability to bind iron molecules and as part of the inflammatory process in fighting bacterial infection. LCN2 is produced by a large variety of cells and was shown to be involved in multiple cancer-related processes.
Prof. Neta Erez says: “Our findings reveal a previously unknown mechanism, mediated by LCN2, which reveals a central role for the mutual interactions between immune cells recruited to the brain (granulocytes) and brain glial cells (astrocytes) in promoting inflammation and in the formation of brain metastases. The findings establish LCN2 as a new prognostic marker and a potential therapeutic target.”