Galectin-1-mediated biochemical controls of melanoma and glioma aggressive behavior

Abstract

Gliomas and melanomas are associated with dismal prognosis because of their marked intrinsic resistance to proapoptotic stimuli, such as conventional chemotherapy and radiotherapy, as well as their ability to escape immune cell attacks. In addition, gliomas and melanomas display pronounced neoangiogenesis. Galectin-1 is a hypoxia-sensitive protein, which is abundantly secreted by glioma and melanoma cells, which displays marked proangiogenic effects. It also provides immune tolerogenic environments to melanoma and glioma cells through the killing of activated T cells that attack these tumor cells. Galectin-1 protects glioma and melanoma cells against cytotoxic insults (including chemotherapy and radiotherapy) through a direct role in the unfolded protein response. Altogether, these facts clearly point to galectin-1 as an important target to be combated in gliomas and melanomas in order to: (1) weaken the defenses of these two types of cancers against radiotherapy, chemotherapy and immunotherapy/vaccine therapy; and (2) reinforce antiangiogenic therapies. In the present article, we review the biochemical and molecular biology-related pathways controlled by galectin-1, which are actually beneficial for melanoma and glioma cells, and therefore detrimental for melanoma and glioma patients.

Keywords: Biochemical pathways; Galectin-1; Glioma; Melanoma.

Figure 1

Major roles of galectin-1 in tumor biology. CD: Cluster of differentiation antigen, could be CD2, CD3, CD7, CD29, CD43 and/or CD45 that are expressed at the cell surface of activated T cell and that display typical β-galactosides recognized by galectin-1.

Figure 2

Processes and pathways mediated by galectin-1 in cancer cell migration. ADM: Adhesion molecules; ADAM-15: Disintegrin and metalloproteinase domain-containing protein 15; ECM: Extracellular matrix; MAP2: Microtubule-associated protein 2; P: Phosphorylation; PKCε: Protein kinase C ε; RhoA: Ras homolog protein, member A GTPase.

Figure 3

Galectin-1-mediated control of angiogenesis. ATF3: Activating transcription factor 3; BEX2: Brain-expressed X-linked 2; CTGF: Connective tissue growth factor; CYR61: Cysteine-rich angiogenic inducer 61; Erk: Extracellular signal-regulated kinase; GRP78 and GRP94: Glucose-regulated protein 78 and 94; IRE1-α: Endoplasmic reticulum to nucleus signaling 1 α; MDG1: Microvascular endothelial differentiation gene 1; Mek: Mitogen-activated protein kinase kinase; ORP150: Oxygen-related protein 150; Raf: Homolog to murine v-raf leukemia oncogene serine/threonine kinase; Ras: Rat sarcoma virus oncogene protein; TF: Transcription factor; VEGF: Vascular endothelial growth factor; VEGFR: VEGF receptor; XBP1: X-box-binding protein 1. EC: Endothelial cell.

Figure 4

How galectin-1 is involved in chemoresistance of cancer cells. ATF3 and ATF6: Activating transcription factor 3 and 6; DUSP5: Dual specificity protein phosphatase 5; GADD153 and GADD45A: Growth arrest and DNA damage inducible protein 153 and 45 α; GRP78 and GRP94: Glucose-regulated protein 78 and 94; HSP70: Heat shock protein 70; IRE1-α: Endoplasmic reticulum to nucleus signaling 1 α; ORP150: Oxygen-related protein 150; PERK: Protein kinase RNA-like endoplasmic reticulum kinase; TF: Transcription factor; XBP1: X-box-binding protein 1.