Abstract
BackgroundInteractions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value.MethodsGene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples.ResultsPlasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels of COL10A1 were detected in patients (p ≤ 0.001), a difference that was driven specifically by females (p < 0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p < 0.001) with good performance in discriminating the two groups (AUC = 0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival.ConclusionSoluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein.
Highlights
Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression
extracellular matrix (ECM)-related gene expression profiles are enriched in lung cancer associated fibroblasts We reasoned that novel potential circulating biomarkers derived from the tumor microenvironment could be developed starting from the discovery of biological pathways defining activated stroma
The ECM3 signature consists of 58 genes encoding 43 structural ECM proteins we found that 11 out the 58 genes were significantly differentially expressed between cancer associated fibroblasts (CAF) and normal counterpart of (NF), each contributing to an enrichment of the ECM3 signature in the activated fibroblasts phenotype (Table 1)
Summary
Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. In the last few years, the concept that each tumor is a complex system composed by both, cancer cells and the surrounding stroma, represented by a variety of cell types such as fibroblasts, immune and endothelial has been well established [11]. This notion has important implications for biomarkers research as novel candidates with diagnostic or prognostic value can potentially be obtained by analyzing molecules produced by stromal cells during their interactions with cancer cells [12, 13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
