Recent research highlights that exosomes derived from obese, insulin-resistant mice differ significantly in their molecular content from those of lean mice, and when these exosomes are taken up by breast cancer cells, they induce changes associated with increased tumor aggressiveness, including a mesenchymal-like state.

Circulating exosomes from visceral adipose tissue and plasma appear to play a crucial role in promoting metastatic and aggressive behaviors in triple-negative breast cancer (TNBC) cells, potentially through pathways involving Rac1, which could serve as a therapeutic target.

Published in BMC Cancer, the study underscores that obesity and high-fat diets can enhance the aggressiveness of TNBC via exosome-mediated mechanisms, revealing new avenues for targeted therapies.

Molecular analyses such as PCR arrays, RNA sequencing, and proteomics identify key pathways activated by exosomal cargo, notably the Rac1 pathway, which is linked to increased cell motility and metastasis.

Bioinformatic analysis shows that TNBC cells exhibit heightened activity of proteins involved in the Rho-GTPase pathway, especially Rac1, which is associated with cancer cell motility and metastatic potential.

TNBC is an aggressive subtype of breast cancer that lacks targeted therapies, relying mainly on chemotherapy, and is characterized by high recurrence rates and lower survival outcomes.

Research explores the therapeutic potential of targeting Rac1 with inhibitors like EHT 1864 to reduce exosome-induced migration and invasion of cancer cells.

The goal of this research is to improve early detection and personalized management of aggressive TNBC, particularly in patients with metabolic diseases, to enhance survival and quality of life.

Findings suggest the potential development of blood tests to detect obesity-derived exosomes as biomarkers for metastatic risk and to target Rho-proteins for inhibiting cancer progression.

Obesity and type 2 diabetes, both linked to systemic inflammation and metabolic dysfunction, are associated with worse cancer outcomes, including in TNBC, which has limited treatment options and poor prognosis once metastasized.

Exosomes are characterized through size exclusion chromatography, electron microscopy, and protein marker analysis, confirming their identity and purity.

Experiments involving the injection of treated cancer cells into healthy models demonstrated increased metastasis to lungs and brains, underscoring the role of obesity-related exosomes in cancer spread.