Abstract
Bone metastases represent the main problem related to the progression of breast cancer, as they are the main cause of death for these patients. Unfortunately, to date, bone metastases are incurable and represent the main challenge for the researcher. Chemokines and cytokines affect different stages of the metastatic process, and in bone metastases, interleukin (IL) -6, IL-8, IL-1β, and IL-11 participate in the interaction between cancer cells and bone cells. This review focuses on IL-11, a pleiotropic cytokine that, in addition to its well-known effects on several tissues, also mediates certain signals in cancer cells. In particular, as IL-11 works on bone remodeling, it plays a relevant role in the osteolytic vicious cycle of bone resorption and tumour growth, which characterizes bone metastasis. IL-11 appears as a candidate for anti-metastatic therapy. Even if different therapeutic approaches have considered IL-11 and the downstream-activated gp130 signaling pathways activated downstream of gp130, further studies are needed to decipher the contribution of the different cytokines and their mechanisms of action in breast cancer progression to define therapeutic strategies.
Highlights
Sossey-AlaouiDespite advances in cancer treatment, therapeutic options for bone metastases are still inadequate and, generally, palliative [1]
In 180 breast cancer patients, interleukin 11 (IL-11) expression level was shown to be significantly increased in the serum of patients with bone metastases compared to patients without metastases, and this is associated with shorter overall survival [76]
IL-11 produced by breast cancer cells induces osteoclast formation genitor cells specify and bythat downregulating granulocyte-macrophage colony-stimulating factor and bone resorption by two mechanisms, the first related to the production of RANKL
Summary
Despite advances in cancer treatment, therapeutic options for bone metastases are still inadequate and, generally, palliative [1]. Considering the bone metastases, interleukin (IL)-6, IL-8, IL-1β, and IL-11 mediate the crosstalk between bone cells and tumour cells acting on bone homeostasis: they show a bone trophic function and are regulators of bone remodelling In this context, the contribution of IL-11 appears peculiar, since it participates in the establishment of a vicious cycle of bone resorption and tumour growth, promoting bone colonization. IL-11 alone stimulates the recovery of platelets after radiation therapy, in mice [13], and its recombinant version has been approved by the FDA to treat radiation-induced thrombocytopenia in tumour patients (e.g., breast cancer) [14] It is involved in myelopoiesis, lymphopoiesis, and erythropoiesis [15]. This review has the aim to take stock of the current knowledge about the role of IL-11 on bone metastasis development to highlight the therapeutic opportunities that the modulation of its activity may offer
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