Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a subpopulation of tumor-associated macrophages

Abstract

High lipoprotein lipase (LPL) activity in non-small cell lung cancer (NSCLC) tissue strongly predicts shorter patient survival. We tested the hypothesis that in NSCLC tissue, macrophages are the major site of LPL expression. LPL expression in the entire NSCLC tissue and in the adjacent non-cancer lung tissue was compared to the expression of genes preferentially expressed in macrophages. LPL expression at the cellular level was analyzed by mRNA fluorescence in situ hybridization. In the whole cancer tissue (but not in the adjacent non-cancer tissue), expression of LPL correlated with expression of genes preferentially expressed in macrophages (MSR1, CD163, FOLR2), but not with expression of genes preferentially expressed in tumor cells. All cells in the cancer and adjacent non-cancer tissue exhibit low LPL expression. However, in cancer tissue only, there were individual highly LPL-expressing cells which were macrophages. These LPL-overexpressing cells were approximately 10 times less abundant than anti-CD163-stained, tumor-associated macrophages. To conclude, in NSCLC tissue, a subpopulation of tumor-associated macrophages highly expresses LPL. Because tumor-associated macrophages are pro-tumorigenic, these cells should be further characterized to better understand the underlying nature of the close relationship between high LPL activity in NSCLC tissue and shorter patient survival.