Clinical relevance of galectin-1 expression in non-small cell lung cancer patients

Background Identification of biomarkers in lung cancer, a leading cause of cancer-related mortality, has a meaningful clinical relevance in the quest of novel prognostic factors and therapeutic targets. The glycan-binding protein galectin-1 (Gal-1) modulates tumor progression by mediating cell–cell and cell–extracellular matrix interactions, as well as angiogenesis and tumor immune-escape. Previous works reported the expression of Gal-1 in lung cancer, although its clinical significance remains uncertain. Objective To assess the clinicopathologic relevance and prognostic value of Gal-1 expression in a cohort of 103 Stage I–III non-small cell lung cancer (NSCLC) patients. Methods Gal-1 expression was determined by immunohistochemistry in tumor tissue samples. The percentage of immunoreactive tumor cells and stroma, as well as the presence of blood vessels with positively stained endothelium in the tumor and surrounding normal tissue, were recorded. Results were correlated with the clinicopathologic factors of the patients (Spearman's rank correlation coefficient, chi-square test) and overall survival by univariate (Kaplan Meier) and multivariate analyses (Cox regression hazard model). Results We did not observe significant associations between Gal-1 expression and relevant clinicopathologic features at diagnosis of NSCLC. However, Kaplan Meier analysis revealed a significant association between Gal-1 expression and overall survival, when Gal-1 expression was analyzed on tumor cells alone (“tumor cell percentage”) or when an integrated score accounting for tumor cell as well as stromal expression of Gal-1 (“total score”) was assessed. Patients showing high Gal-1 expression evidenced a poorer clinical outcome. Furthermore, “total score” remained significantly associated with survival by multivariate Cox regression analysis in the whole cohort of patients, even when controlling for the classical predictors and prognostic factors of NSCLC. Conclusion We conclude that Gal-1 expression may be a useful biomarker for better prediction of the clinical outcome and management of NSCLC patients.Fil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roitman, Pablo. Hospital Italiano de Buenos Aires; ArgentinaFil: Nuñez, Myriam. Hospital Italiano de Buenos Aires; ArgentinaFil: Pallota, María Guadalupe. Hospital Italiano de Buenos Aires; ArgentinaFil: Boggio, Gastón. Hospital Italiano de Buenos Aires; ArgentinaFil: Smith, David. Hospital Italiano de Buenos Aires; ArgentinaFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

TGF-beta specifically enhances the metastatic attributes of murine lung adenocarcinoma: implications for human non-small cell lung cancer

Lung cancer is the most frequent and one of the most deadly cancer types and is classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Transforming growth factor beta (TGFb) regulates a wide array of cell functions and plays a major role in lung diseases, including NSCLC. TGFb signals through the complex of TGFb type I and type II receptors, triggering Smad and non-Smad signaling pathways such as PI3K/Akt and MEK1/ERK. We investigated the role of TGFb1 on the progression of the murine lung adenocarcinoma cell line LP07. Furthermore, we undertook a retrospective study with tissue samples from stage I and II NSCLC patients to assess the clinical pathologic role and prognostic significance of TbRI expression. We demonstrated that although lung cancer cell monolayers responded to TGFb1 anti-mitogenic effects and TGFb1 pulse (24 h treatment) delayed tumor growth at primary site; a switch towards malignant progression upon TGFb1 treatment was observed at the metastatic site. In our model, TGFb1 modulated in vitro clonogenicity, protected against stress-induced apoptosis and increased adhesion, spreading, lung retention and metastatic outgrowth. PI3K and MEK1 signaling pathways were involved in TGFb1-mediated metastasis stimulation. Several of these TGFb responses were also observed in human NSCLC cell lines. In addition, we found that a higher expression of TbRI in human lung tumors is associated with poor patient’s overall survival by univariate analysis, while multivariate analysis did not reach statistical significance. Although additional detailed analysis of the endogenous signaling in vivo and in vitro is needed, these studies may provide novel molecular targets for the treatment of lung cancer.Fil: Vazquez, Paula Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Daroqui, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas, Argentina; Montefiore Medical Center. Department of Oncology; Estados Unidos de América;Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Dalurzo, Mercedes Liliana. Hospital Italiano de Buenos Aires; Argentina;Fil: Smith, David Eduardo. Hospital Italiano de Buenos Aires; Argentina;Fil: Grasselli, Julieta. Hospital Italiano de Buenos Aires; Argentina;Fil: Pallota, Maria Guadalupe. Hospital Italiano de Buenos Aires; Argentina;Fil: Ehrlich, Marcelo. Tel Aviv University. George S. Wise Faculty of Life Sciences. Department of Neurobiochemistry; Israel;Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina