Galectin-1 links tumor hypoxia and radiotherapy

Abstract

Radiation therapy is a main stay in treating solid tumors and plays a significant role in definitive and adjuvant therapy. Unfortunately, local control remains a challenge, in which the success of radiotherapy is largely dictated by tumor hypoxia, DNA damage repair and the antitumor immune response. Extensive efforts have therefore been devoted to targeting the factors that attenuate tumor radiosensitivity, although with limited success. Mounting evidence suggests that tumor and endothelial cells may utilize galectin-1 (Gal-1) for protection against radiation through several mechanisms. Targeting Gal-1 in combination with radiotherapy provides an exciting approach to address several radiation-prohibitive mechanisms.

Keywords: galectin-1; radiotherapy; tumor hypoxia.

Fig. 1.

Gal-1 modulation of tumor radiation response. Gal-1 expression increases in the presence of hypoxia and after tumor irradiation. This elevation of Gal-1 increases repair of radiation-induced DNA damage through H-Ras signaling to promote cell survival. The HIF1/Gal-1/H-Ras interaction may form a positive feedback loop promoting HIF1 transcriptional activity to drive aggressive tumor phenotypes and radiation resistance. Hypoxia also increases Gal-1 to EC binding to mediate proangiogenic signaling. Gal-1 also induces the apoptosis of effector T cells while promoting Treg expansion to create tumor immune privilege.