title: Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration.
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.
authors: Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey, United States of America.
authors: Jhon Alberto
authors: JA
authors: Ochoa-Alvarez
authors: Harini
authors: H
authors: Krishnan
authors: Yongquan
authors: Y
authors: Shen
authors: Nimish K
authors: NK
authors: Acharya
authors: Min
authors: M
authors: Han
authors: Dean E
authors: DE
authors: McNulty
authors: Hitoki
authors: H
authors: Hasegawa
authors: Toshinori
authors: T
authors: Hyodo
authors: Takeshi
authors: T
authors: Senga
authors: Jian-Guo
authors: JG
authors: Geng
authors: Mary
authors: M
authors: Kosciuk
authors: Seung S
authors: SS
authors: Shin
authors: James S
authors: JS
authors: Goydos
authors: Dmitry
authors: D
authors: Temiakov
authors: Robert G
authors: RG
authors: Nagele
authors: Gary S
authors: GS
authors: Goldberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D029901:Maackia / Q000737:chemistry; D008545:Melanoma / Q000098:blood supply / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009336:Necrosis / Q000139:chemically induced; D009389:Neovascularization, Pathologic / Q000178:diet therapy; D037121:Plant Lectins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; D019158:N-Acetylneuraminic Acid; D037121:Plant Lectins; D019061:src-Family Kinases; C490441:Pdpn protein, mouse; D000098853:Podoplanin