Altered Fat Cells May Fuel Breast Cancer Tumor Growth
Researchers have hypothesized that altered fat cells may fuel the growth of breast cancer tumors. They identified three genes that can induce tumor growth: IL-6, IL-8, and IL-10. They then studied their interaction with BC cells to determine whether they contribute to CAF expansion.
The presence of hypoxia in the human breast may contribute to the growth of tumor cells. It may affect the TCA cycle and inhibit the electron transport chain. It may also confer stemness. This hypothesis suggests the need for antiangiogenic therapy in conjunction with antioxidant modulator therapy. But how can hypoxia contribute to the growth of breast tumor cells?
Specifically, hypoxia is known to stimulate the growth of tumor cells by activating genes related to angiogenesis, anaerobic glycolysis, invasion, and metastasis. This process is important in breast cancer because hypoxia promotes breast tumor growth in both the primary and metastatic sites. The expression of HIF-1a has been associated with a poor prognosis in BC patients.
Recent evidence indicates that IL-6 is a potential fuel for breast cancer tumor growth. IL-6 is upregulated in breast cancer stem tumorigenic cells, and it has been linked to poor prognosis. It has also been suggested that stem/progenitor cells may contribute to the development of breast cancer in vivo. These cells express high levels of IL-6 mRNA and have high levels of Notch-3.
IL-6 has been implicated in cancer stem cells, which are highly resistant to conventional therapy. Moreover, IL-6 can induce immunosuppression and help cancer cells resist therapy. Neutralization of IL-6 might reverse this resistance. The anti-IL-6R antibody tocilizumab has shown promising results when used alone or in combination with chemotherapy. However, there is some controversy regarding the use of IL-6 neutralization in combination with immune checkpoint inhibitors. In addition, neutralizing IL-6 may help counteract the cytokine release syndrome that can occur in patients receiving immunotherapies.
Inhibition of IL-8 activity by cancer-related tumor cells has the potential to suppress tumor-promoting signaling pathways. These pathways include angiogenesis and neutrophil-derived suppressor cells. In addition, blocking IL-8 may inhibit bulk tumor growth. In vitro experiments suggest that IL-8 can promote tumor growth through autocrine and paracrine mechanisms.
In addition, IL-8 has been shown to induce EMT in breast cancer cells, colon cancer cells, and nasopharyngeal cancer cells. In breast cancer cells, IL-8 induces EMT via the PI3K-AKT/MEK-ERK pathways. Cancer cells require the mesenchymal-epithelial transition to progress. However, the IL-8-mediated EMT can be suppressed by neutralizing cytokines.
In breast cancer, IL-10 stimulation may be a key factor in tumor growth. Inhibitors and agonists of IL-10 may be effective therapeutic tools in treating this disease. Moreover, certain IL-10 polymorphisms may contribute to susceptibility to breast cancer.
In animal models, interleukin-10 (IL-10) suppresses the growth of tumor cells and has antitumor effects. Its effects may stem from its ability to inhibit angiogenesis and inhibit the expression of several growth factors. Moreover, IL-10 also promotes B-cell differentiation and immune-globulin secretion. In addition, IL-10 promotes the production of anti-CTLs, which are important for anti-tumor immunity.
Interleukin-13 (IL-13) is a member of the superfamily of pleiotropic cytokines that play a central role in inflammation and the regulation of immune responses. IL-13 can stimulate the expression of several key target genes in the immune system, including IL-4 and CD36. In cancer cells, IL-13 has diverse effects, including regulating tumorigenesis and tumor metastasis.
In addition to regulating cancer invasion and metastasis, IL-13 is associated with a poor prognosis in breast cancer patients with increased levels of IL13Ra2. It is also involved in breast cancer metastasis to the lung and liver. In fact, a recent study found that overexpression of IL13Ra2 was associated with poor patient survival. In addition, depletion of IL13Ra2 significantly decreased primary tumor growth and lung metastasis formation.