Lung Adenocarcinoma Cell Sensitivity to Chemotherapies: A Spotlight on Lipid Droplets and SREBF1 Gene.

To explore the relationship between cancer cell SREBF1 expression, lipid droplets (LDs) formation, and the sensitivity to chemotherapies, we cultured lung adenocarcinoma cells H1299 (with LD) and H1563 (without LD) in a serum-free basal medium (BM) or neutrophil degranulation products containing medium (NDM), and tested cell responses to cisplatin and etoposide. By using the DESeq2 Bioconductor package, we detected 674 differentially expressed genes (DEGs) associated with NDM/BM differences between two cell lines, many of these genes were associated with the regulation of sterol and cholesterol biosynthesis processes. Specifically, SREBF1 markedly declined in both cell lines cultured in NDM or when treated with chemotherapeutics. Despite the latter, H1563 exhibited LD formation and resistance to etoposide, but not to cisplatin. Although H1299 cells preserved LDs, these cells were similarly sensitive to both drugs. In a cohort of 292 patients with non-small-cell lung cancer, a lower SREBF1 expression in tumors than in adjacent nontumor tissue correlated with overall better survival, specifically in patients with adenocarcinoma at stage I. Our findings imply that a direct correlation between SREBF1 and LD accumulation can be lost due to the changes in cancer cell environment and/or chemotherapy. The role of LDs in lung cancer development and response to therapies remains to be examined in more detail.

Potential Roles of Acute Phase Proteins in Cancer: Why Do Cancer Cells Produce or Take Up Exogenous Acute Phase Protein Alpha1-Antitrypsin?

An association between acute-phase proteins (APPs) and cancer has long been established and there are numerous reports correlating altered levels and/or molecular forms of APPs with different types of cancers. Many authors have shown a positive correlation between high levels of APPs, like alpha1-antitrypsin (AAT), and unfavorable clinical outcome in cancers. Conversely, others proposed that high levels of APPs are probably just a part of nonspecific inflammatory response to cancer development. However, this might not be always true, because many cancerous cells produce or take up exogenous APPs. What is the biological significance of this and what benefit do cancer cells have from these proteins remains largely unknown. Recent data revealed that some APPs, including AAT, are able to enhance cancer cell resistance against anticancer drug-induced apoptosis and autophagy. In this review, we specifically discuss our own findings and controversies in the literature regarding the role of AAT in cancer.