Prevalence of Primary Liver Cancer is Affected by Place of Birth in Hispanic People Residing in the United States: All of Us Research Program Report.

BACKGROUND: Hispanic individuals have a disproportionately higher incidence and mortality for stomach, cervix, and liver cancers compared to Non-Hispanic White people. Since disparities in cancer incidence are influenced by multiple factors including immigration, elucidating the effect of birthplace and exposure to risk factors on the prevalence of these cancers is crucial for identifying high-risk populations and target risk reduction interventions. METHODS: The National Institutes of Health All of Us Research Program is a prospective, multidimensional biomedical data resource of underrepresented, minoritized people. The Registered Tier Dataset v5 was utilized to evaluate the prevalence and risk of stomach, cervix, and liver cancers among United States (US) born and non-US born Hispanic participants. RESULTS: Of over 434 000 current participants, 60 540 are Hispanic; 30 803 (50.9%) reported being US born and 29 294 (48.4%) non-US born. Non-US born Hispanic participants had significantly higher prevalence (.39% vs .21%, P < .001) and associated risk (OR 1.84, 95% CI 1.29-2.64, P < .001) of liver cancer, and trend towards higher prevalence of stomach (.14% vs .09%, P = .076) and cervix cancers (.27% vs .20%, P = .083) compared to US born counterparts. US born Hispanic patients with these 3 cancers were significantly younger than non-US born cohort (mean age 56.8 vs 61.7 years, P < .001). DISCUSSION: This is the first report using All of Us data to show that non-US born Hispanic participants have a higher risk of liver cancer compared to US born participants. Further analyses, including genomic studies, are necessary to understand these differences and identify targets for risk reduction interventions.

Internalization of Exosomes through Receptor-Mediated Endocytosis.

The tumor microenvironment is replete with factors secreted and internalized by surrounding cells. Exosomes are nano-sized, protein-embedded, membrane-bound vesicles that are released in greater quantities from cancer than normal cells and taken up by a variety of cell types. These vesicles contain proteins and genetic material from the cell of origin and in the case of tumor-derived exosomes, oncoproteins and oncogenes. With increasing understanding of the role exosomes play in basic biology, a more clear view of the potential exosomes are seen to have in cancer therapeutics emerges. However, certain essential aspects of exosome function, such as the uptake mechanisms, are still unknown. Various methods of cell-exosome interaction have been proposed, but this review focuses on the protein-protein interactions that facilitate receptor-mediated endocytosis, a broadly used mechanism by a variety of cells.

Exosomal survivin facilitates vesicle internalization.

Survivin, a member of the inhibitor of apoptosis (IAP) protein family plays a significant role in cell fate and function. It is significantly overexpressed in tumor cells and has been identified in most cancer cell types. A novel extracellular population has recently been identified and its function is still unknown. Emerging evidence continues to shed light on the important role the tumor microenvironment (TME) has on tumor survival and progression. This new population of survivin has been seen to enhance the tumor phenotype when internalized by recipient cells. In this paper, we sought to better understand the mechanism by which survivin is taken up by cancer cells and the possible role it plays in this phenomenon. We isolated the exosomal carriers of extracellular survivin and using a lipophilic stain, PKH67, we tracked their uptake with immunofluorescence and flow cytometry. We found that by blocking exosomal survivin, exosome internalization is reduced, signifying a novel function for this protein. We also discovered that the common membrane receptors, transferrin receptor, endothelin B receptor, insulin receptor alpha, and membrane glucocorticoid receptor all facilitate exosomal internalization. This understanding further clarifies the protein-protein interactions in the TME that may influence tumor progression and identifies additional potential chemotherapeutic targets.