Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: Gene expression associated with metastatic potential in human lung cancer

Abstract

Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

Cortical gene expression correlates of temporal lobe epileptogenicity

“…Increased expression of HS3ST3A1 has been reported in glioblastoma multiforme cell lines [68]. Additionally, heparin sulfate cleavage by heparanase is involved in metastatic cell dissemination, angiogenesis and inflammation [66]. Upregulation of HS3ST3A1 in a highly metastatic subline of lung cancer, PC14HM, is thought to increase 3-O-sulfated heparin sulfate biosynthesis, increasing the metastatic potential [66].…”

“…Additionally, heparin sulfate cleavage by heparanase is involved in metastatic cell dissemination, angiogenesis and inflammation [66]. Upregulation of HS3ST3A1 in a highly metastatic subline of lung cancer, PC14HM, is thought to increase 3-O-sulfated heparin sulfate biosynthesis, increasing the metastatic potential [66]. HS3ST3A1 expression of its glycocalyx transcript is reduced in pre-eclamptic placental tissue and is positively correlated with maternal blood pressure and neonatal birth weight [69].…”

“…The heparin sulfate gene HS3ST3A1 encodes for a specific subtype of heparin sulfate (HS), 3-O-sulfated heparin sulfate [66]. Increased expression of HS3ST3A1 is related to pathogenesis of recurrent respiratory papillomatosis and may be involved in the transition from Human Papilloma Virus infection to tumorigenesis [67].…”

The role of endocytic Rab GTPases in regulation of growth factor signaling and the migration and invasion of tumor cells

“…Furthermore, in highly metastatic lung cancer, post-translational modifications and in increase in gene expression mediated elevated Rab37 and Rab7 levels. 86,87 In liver cancer, Rab1b, Rab4b, Rab10, Rab22, and Rab24 are overexpressed 88 while Rab1a is higher in tongue cancer. 89 Rab2B levels are elevated in colon carcinoma 90 while in thyroid-associated adenomas; Rab5a and Rab7 are upregulated.…”

Upregulation of Nuclear Heat Shock Factor 1 Contributes to Tumor Angiogenesis and Poor Survival in Patients With Non–Small Cell Lung Cancer

“…Approximately 40% of patients with NSCLC die of recurrence or metastasis within 5 years after potentially curative resection. Owing to the discovery of tumor biomarkers, advanced molecular targeted therapy brings hope [7,8]. However, further studies are required to discover and identify novel and specific biomarkers of NSCLC for benefit in patient survival and quality of life.…”