The aggressiveness of murine lymphomas selected in vivo by growth rate correlates with galectin-1 expression and response to cyclophosphamide

Abstract

Although lymphomas account for almost half of blood-derived cancers that are diagnosed each year, the causes of new cases are poorly understood, as reflected by the relatively few risk factors established. Galectin-1, an immunoregulatory ß-galactoside-binding protein, has been widely associated with tumor-immune escape. The aim of the present work was to study the relationship between tumor growth rate, aggressiveness, and response to cyclophosphamide (Cy) therapy with regard to Gal-1 expression in murine T-cell lymphoma models. By means of a disruptive selection process for tumor growth rate, we generated two lymphoma variants from a parental T-cell lymphoma, which have unique characteristics in terms of tumor growth rate, spontaneous regression, metastatic capacity, Gal-1 expression and sensitivity to Cy therapy. Here, we show that Gal-1 expression strongly correlates with tumor growth rate, metastatic capacity and response to single-dose Cy therapy in T-cell lymphoma models; this association might have important consequences for evaluating prognosis and treatments of this type of tumors.

Galectins and their ligands: negative regulators of anti-tumor immunity

“…Gal-1-driven immunoregulation in the cancer microenvironment has been fully documented in several syngeneic murine models of melanomas, lymphomas, and lung carcinomas; where knocking down tumor-derived Gal-1 resulted in significant tumor rejection mediated by higher expression of IFN-γ [22, 28, 29]. Similarly, the immune escape of Hodgkin’s lymphoma has been associated with increased Gal-1 levels that determine a predominant Th2 cytokine signature, accompanied by a greater presence of Tregs [25].…”

Study of Galectins in Tumor Immunity: Strategies and Methods

“…Galectin-1 expression correlates with tumor burden and adverse clinical features in several tumor types including laryngeal squamous cell carcinoma [16], prostate adenocarcinoma [17], colon adenocarcinoma [18,19], ovarian carcinoma [20,21], breast carcinoma [14,22], melanoma [23], Hodgkin lymphoma [24,25], cervical cancer [26], T cell lymphoma [27], pancreatic ductal adenocarcinoma [28], neuroblastoma [29], hepatocellular carcinoma [30,31], chronic lymphocytic leukemia [32], glioblastomas [33,34], MLL-rearranged B lymphoblastic leukemias [35], and thyroid carcinoma [36].…”