Using HMGB1 Protein as a Surrogate Marker for Lung Cancer in High‐Risk Populations

Abstract

Lung cancer is the leading cause of cancer‐related death, independent of gender or ethnicity, with a 5‐year overall survival of 17.1%. Although screening protocols for early detection exist, lung cancer is often diagnosed at an advanced stage. This is due, in part, to many patients experiencing barriers to healthcare access which contribute to delays in diagnosis. Supra‐normal biosynthesis of saturated (SFA) and unsaturated fatty (UFA) acids is a hallmark of cancer. In fact, several lines of evidence demonstrate that increased lipid desaturation by stearoyl‐CoA desaturase (SCD1) promotes lung cancer growth. We hypothesize that increased intracellular UFA, such as oleate (OA), promotes cancer cell growth by reducing cancer associated inflammation. To test this hypothesis we evaluated the effect of OA and inhibition of OA synthesis on proinflammatory High Mobility Group Box Protein 1 (HMGB1). Decreasing OA synthesis reduced intracellular HMGB1 expression, but increased its release from cells. Given our data, alterations in OA levels appear to have a substantial effect on localization of HMGB1. Further work is necessary to define the connections between SCD1, OA and HMGB1 release in lung cancer cells. This knowledge will provide insight into how fat regulates cancer development.Support or Funding InformationThe University of Minnesota School of Medicine New Faculty Start up and College of Saint Scholastica McNair Scholars Program.