Increased expression of the LGALS3 (Galectin 3) gene in human non–small‐cell lung cancer

Abstract

Patients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti-metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome-wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the beta-galactoside-binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real-time quantitative reverse transcription-polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10/30) of the non-small-cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small-cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in non-small-cell lung cancer (3.065 +/- 3.976) was significantly higher than those of small-cell lung cancer (0.02 +/- 0.03) (P < 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non-small-cell lung cancer that overexpresses Galectin 3, but not in small-cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small-cell lung cancer and may represent a novel target molecule in non-small-cell lung cancer therapy.

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

“…36 Nonsmall cell lung cancers were seen to harbor increased levels of galectin-3 mRNA when compared to normal epithelial cells. 27 In the present study, we observed different patterns of galectin-3 expression between squamous cell carcinomas and adenocarcinomas. Squamous cell carcinomas express galectin-3 predominantly in the cytoplasm of well-differentiated areas with rare nuclear staining.…”

“…21 What is particularly intriguing about this sole chimera-type galectin is its presence in nuclear, cytoplasmic and extracellular sites, 22 its ability to interact with a variety of carbohydrate and protein ligands and to form pentamers with unique crosslinking abilities, 23 its strong antiapoptotic activity coupled with the nuclear export of the phosphorylated form (for example in chemotherapeutic treatment), 24 and its effect on promoter activity of cyclin D1, 25 which is a prognostic marker in the adenocarcinoma subgroup of lung carcinomas. 26 Alteration of galectin-3 expression in lung carcinomas [27][28][29] and a high level of galectin-3 in the sera of lung carcinoma patients 30 have already been observed. However, a comprehensive analysis of the potential prognostic value of galectin-3 has not yet been carried out on a large series of lung carcinoma patients.…”

Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD

“…A recent study showed that galectin-3 is mitogenic for cardiac fibroblasts, induces collagen deposition and may lead to ventricular dysfunction [25]. In the lung, epithelial expression of galectin-3 is increased in nonsmall lung cancer [26,27], while in murine asthma models, gene therapy targeted to galectin-3 inhibits allergen-induced airway inflammation, including IL-5 expression, and epithelial mucous metaplasia [28][29][30]. Secretion of galectin-3 is also upregulated in a rat model of radiation-induced lung fibrosis [31,32].…”

DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities and promotes cancer cell growth

“…Lung cancer is characterized by its high metastatic potential and, therefore, a complete cure for patients suffered from lung cancer is quite difficult despite a host of intervention approaches. 2 Thus, it is beneficial to the patients to diagnose the cancer at an earlier stage before it starts to disseminate and to establish more effective therapies specifically designed for lung cancer.…”