Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration

Jhon Alberto Ochoa-Alvarez, Harini Krishnan, Yongquan Shen, Nimish K. Acharya, Min Han, Dean E. McNulty, Hitoki Hasegawa, Toshinori Hyodo, Takeshi Senga, Jian Guo Geng, Mary Kosciuk, Seung S. Shin, James S. Goydos, Dmitry Temiakov, Robert G. Nagele, Gary S. Goldberg

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors that have not been identified. We report here that a lectin from the seeds of Maackia amurensis (MASL) with affinity for O-linked carbohydrate chains containing sialic acid targets PDPN to inhibit transformed cell growth and motility at nanomolar concentrations. Interestingly, the biological activity of this lectin survives gastrointestinal proteolysis and enters the cardiovascular system to inhibit melanoma cell growth, migration, and tumorigenesis. These studies demonstrate how lectins may be used to help develop dietary agents that target specific receptors to combat malignant cell growth.

Original languageEnglish (US)
Article numbere41845
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 23 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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