Breast cancer occurs more frequently and is more progressive in obese patients, according to a new study from an international team of researchers who found that the fat around tumors aids in the expansion and invasion of cancer stem cells (CSCs), which are responsible for the growth of tumors.
Cancer stem cells are a small subset of cells within tumors that are responsible for metastasis and allow cancers to spread and form in several organs of the body. Because conventional chemotherapy and radiotherapy are not able to eliminate CSCs, a relapse often occurs after the first successful treatment.
The influence of obesity on cancer morbidity and mortality is supported by the research — specifically, that up to 20 percent of cancer-related deaths may be associated with obesity. Obese women are at greater risk of developing breast cancer after menopause, and they experience a worse progression of the disease, regardless of age. The mechanisms by which obesity leads to the development of cancer still remain unclear. Obesity-related fat can be responsible for local inflammation and can prevent adipocytes, cells that primarily compose adipose tissue, from maturing.
In the study titled “Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b–Mediated Malignant Progression,” published in Cancer Research, researchers cultured adipocytes and breast cancer cells together and observed their effect on tumor aggressiveness, capacity of local invasion, and metastatic potential.
The scientists revealed that the interaction between tumor cells and immature adipocytes over the first phases of breast cancer development caused increased secretion of cytokines, which are proinflammatory regulatory proteins. “Cytokines cause a greater expansion of highly metastatic CSCs,” study author Juan Antonio Marchal Corrales said in a press release.
The authors also described the underlying mechanism by which this phenomenon occurs, and its association with the activation of the SRC kinase protein, which in turn activates the Sox2 transcription factor (essential to maintain stem cells characteristics) and a small RNA molecule, miRNA-302b.
“The prolonged coculture of tumor cells with immature adipocytes or cytokines increased the proportion of CSCs (which had the ability to form new tumors), the presence of tumor cells in blood, and the metastatic potential after its implementation in mice,” Marchal said. “And last, we found that SRC-Kinase-inhibiting drugs decrease the production of cytokines and CSCs.”
These observations can explain the increased rate of breast cancer mortality in obese patients and provide a novel preclinical rationale to investigate the efficacy of SRC inhibitors for breast cancer therapy.