Polymeric immunoglobulin receptor boosts cancer stemness, tumorigenesis in HCC patients

Extracellular vesicles (EVs) enriched with the polymeric immunoglobulin receptor (pIgR) molecule contributes to tumorigenesis and cancer stemness in patients with hepatocellular carcinoma (HCC), reports a recent study.

The study included serum samples from healthy donors without liver diseases, individuals with chronic hepatitis B virus infections, and untreated patients with liver diseases such as cirrhosis and early and late HCC. EVs were isolated from the sera and subjected through various functional assays. A proteomic analysis was also conducted to determine the components of EVs.

In addition, quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and other immune-based assays were used to quantify EV pIgR levels, comparing between tumour and nontumour tissues in HCC patients.

Researchers found that patients with late HCC had circulating EVs with heightened expression levels of pIgR as compared with healthy controls. Moreover, EVs from late HCC patients showed the highest potency in promoting tumour cell migration, invasiveness, and colony formation, as well as promoted tumour development in recipient cells.

Notably, an anti-pIgR neutralizing antibody attenuated the augmenting effect of late HCC EVs on cancer stemness and tumorigenesis.

“Herein, we demonstrated that nanometre-sized extracellular vesicles released by tumours promote cancer stemness and tumorigenesis. Within these oncogenic vesicles, we identified a key component that functions as a potent modulator of cancer aggressiveness,” the researchers said.

“By inhibiting this functional component of EVs using a neutralizing antibody, tumour growth was profoundly attenuated in mice. This hints at a potentially effective therapeutic alternative for patients with cancer,” they added.