BEL β-Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

Abstract

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients’ survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen–Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL β-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL β-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL β-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL β-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL β-trefoil can be considered an effective biomolecule to counteract melanoma disease.

Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling

“…Different lectins with b-trefoil folding were reported to have antitumor effects both in cell lines (Bovi et al, 2013) and in a melanoma xenografted zebrafish model (Valenti et al, 2020) and to induce apoptosis with the activation of MAPK and stressactivate kinase pathways in addition to NF-kB (Hasan et al, 2019). Moreover, it was previously shown that TNF-a-mediated signaling pathway and apoptosis can be elicited in hematological cells by several lectins upon binding to surface receptors, like globotriaosylceramide (Gb3) carbohydrate chain (Hosono et al, 2014;Liao et al, 2016;Chernikov et al, 2017), which is also a known receptor for Shiga toxins (Lee et al, 2015).…”

Fisetin: An Integrated Approach to Identify a Strategy Promoting Osteogenesis

“…As in mammals, three stages can be recognized in the osteogenic differentiation: an early stage characterized by runx2a and runx2b expression; an intermediate stage characterized by osterix gene expression; and a maturation stage characterized by the expression of osteocalcin, osteonectin, collagens, and other bone matrix genes ( Li et al, 2009 ; Knopf et al, 2011 ). Zebrafish has been proposed as a useful in vivo model for studying cell signaling in bone ( Valenti et al, 2020a ) and for evaluating the effects of bone treatments ( Valenti et al, 2020b ). Zebrafish are frequently used in developmental biology ( Suniaga et al, 2018 ).…”

The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

“…Other tested compounds using zebrafish models were recently demonstrated to possess antimelanoma potential. Among them are diphlorethohydroxycarmalol [286], theaflavin [287], ellagic acid [288], inularin [289], and BEL β-trefoil [290].…”