Obesity Fuels Breast Cancer Spread Through a Distinct Molecular Pathway
Obesity may be linked to a unique molecular mechanism that causes early-stage, premalignant breast lesions to progress to invasive breast cancer. Researchers, including those from the University of Oklahoma Health Campus in the United States, reported that tumors from obese patients showed a unique stress-adaptive phenotype rather than just an increased activation of classical invasive pathways.
A key component of targeted cancer prevention and the creation of innovative treatments to lower the incidence and severity of breast cancer is an understanding of the role obesity plays in the pathophysiology of the disease. Type 2 diabetes and obesity are regarded as chronic inflammatory conditions.
Although lowering inflammation is thought to have a protective impact, lowering reactive oxygen species (ROS) is controversial in the treatment of breast cancer because ROS are necessary for the death of tumor cells. Therefore, more research is needed to determine how the widely distributed antioxidant glutathione in its reduced state (GSH) can be used to treat breast cancer. According to them, metabolic stress adaption, inflammation, and remodeling of the tumor microenvironment may drive a fundamentally distinct invasive program for tumors that arise in an obese context.
The body's physiological responses to disturbances in cell energy, nutrition, or oxygen levels are referred to as metabolic stress adaption. According to the team, roughly 25% of all newly discovered breast lesions are ductal carcinoma in situ (DCIS), also known as stage 0, which has a higher lifetime risk of developing invasive ductal carcinoma (IDC). But not every DCIS lesion develops into IDC.
One significant and rising risk factor for breast cancer is obesity. According to the researchers, the precise molecular processes by which obesity affects the development of early-stage, premalignant breast lesions into invasive breast cancer are still unknown. Determining which lesions are most likely to develop into invasive breast cancer is a major therapeutic problem in DCIS so that patients are not overtreated or undertreated, according to principal investigator Elizabeth A. Wellberg of the University of Oklahoma Health Campus' department of pathology.
Our work examined how obesity modifies the molecular characteristics linked to breast cancer invasion using spatial transcriptome profiling of epithelial, stromal, and immunological compartments from DCIS and IDC lesions in obese and non-obese patients, according to Wellberg. One method for mapping gene expression is spatial transcriptomic profiling.
They stated, "Conversely, the obese setting was characterised by a distinct stress-adaptive phenotype, enriched for metabolic adjustment, oxidative stress response, and inflammatory signalling. "Increased expression of the enzyme "sulfatase 2" (SULF2) accompanied the outcome, indicating that obesity may affect both tumor biology and prognostic interpretation, according to the team. SULF2 is frequently a therapeutic target and has a significant role in the development of cancer. The results imply that invasive risk in obese patients may not be well captured by conventional prognostic methods .According to the researchers, risk stratification and patient treatment could be enhanced by incorporating immunological composition, metabolic health, and genomic characteristics linked to obesity into diagnostic and prognostic models.
According to estimates, a woman's lifetime risk of having breast cancer is 12.9%. Breast cancer is the most prevalent cancer diagnosed in women worldwide.
