Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma

Abstract

Brain metastases (BM) are the most common brain tumors of adults and are associated with fatal prognosis. Formation of new blood vessels, named angiogenesis, was proposed to be the main hallmark of the growth of BM. Previous preclinical evidence revealed that angiogenic blockage might be considered for treatment; however, there were varying responses. In this study, we aimed to characterize the expression pattern of angiogenesis-related genes in BM of lung cancer and melanoma, which might be of importance for the different responses against anti-angiogenic treatment. Fifteen snap-frozen tissues obtained from BM of non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and melanoma patients were analyzed for angiogenesis-related genes using a commercially available gene expression kit. Epilepsy tissue was used as control. Expression values were analyzed using hierarchical clustering investigating relative fold changes and mapping to Omicsnet protein interaction network. CXCL10, CEACAM1, PECAM1, KIT, COL4A2, COL1A1, and HSPG2 genes were more than 50-fold up-regulated in all diagnosis groups when compared to control, whereas genes such as ANGPT4, PDGFRB, and SERPINF1 were down-regulated only in SCLC and melanoma groups, respectively. Using hierarchical clustering, 12 out of 15 cases were allocated to the correct histological primary tumor type. We identified genes with consistent up-regulation in BM of lung cancer and melanoma and other genes with differential expression across BM of these tumor types. Our data may be of relevance for targeted therapy or prophylaxis of BM using anti-angiogenic agents.

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

“…Kienast et al noted that the human melanoma cell line they injected intracardially, MDA-MB-435, lacked VEGF-A expression, suggesting that other mechanisms of vessel co-option and angiogenesis may be present and utilized by melanoma cells. A recent analysis of angiogenesis-related gene expression in human brain melanoma metastases documented a more than 50-fold increase in C-X-C motif chemokine ligand 10 (CXCL10), carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), platelet and endothelial cell adhesion molecule 1 (PECAM1), cluster of differentiation 117 (CD117/KIT), collagen type IV alpha 2 (COL4A2), collagen type I alpha 1 (COL1A1), and heparan sulfate proteoglycan 2 (HSPG2) [ 71 ]. However, to what extent these genes contribute to neovascularization in melanoma brain metastases formation will require additional studies.…”

siRNA-Mediated suppression of collagen type iv alpha 2 (COL4A2) mRNA inhibits triple-negative breast cancer cell proliferation and migration

“…In addition, COL4A2 is significantly overexpressed in tissues obtained from brain metastases of lung cancer and melanoma patients [19]. Oktem G found a high level of COL4A2 when cancer stem cells (CSC) were maintained as serum-grown prostate CSC spheroids [20].…”

Identification of miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma

“…miR-486-5p is significantly downregulated in PCT tissues and cell lines and its underexpression promotes cell proliferation and represses cell apoptosis in PTC (22). It is reported that miR-486-5p is downregulated in lung adenocarcinoma and COL4A2 is upregulated in non-small cell lung cancer and small cell lung cancer (23,25). COL4A2, encodes for the collagen type IV alpha 2 chain, and is the subunit of type IV collagen, which is the major structural component of basement membranes.…”