title: Diverse pathological implications of YKL-40: answers may lie in 'outside-in' signaling.
abstract: The developing paradigms about YKL-40, a member of the "mammalian chitinase-like proteins", from across the globe, project it as a vital parameter for the detection of disease onset and progression. It is expressed and secreted by cancer cells of different origins along with a variety of non-malignant cells including inflammatory and structural cells. Numerous studies demonstrate that YKL-40 over-expression is associated with increased patient mortality though the cellular receptors responsible for mediating these effects have not yet been identified. The putative YKL-40 ligands are thought to be carbohydrate structures, since it is capable of binding chitin, chito-oligosaccharides and heparin. Binding of collagen to YKL-40, identified it as the only non-carbohydrate extracellular matrix (ECM) ligand for YKL-40. Our broad understanding of YKL-40 as a versatile biomarker and its involvement in activating several signaling pathways make us anticipate that its specific receptors/binding partners may exist on the cell surface also. The cell surface heparan sulfate (HS) moieties seem to be the potential candidates for this role, suggesting that it could interact with HS-proteoglycans. It is recommended to clearly delineate YKL-40-mediated signaling mechanisms before promoting the YKL-40 know-how for translational research, in both diagnostic and therapeutic applications. The present review provides an overview of YKL-40 as a versatile biomarker, discussing the related pathological mechanisms and aims to reassess and unify the already proposed diverse hypotheses in YKL-40-regulated signaling mechanisms.
authors.affiliation: Dr. D. Y Patil Biotechnology & Bioinformatics Institute, Tathawade, Dr. D. Y. Patil Vidyapeeth, Pune, India. maansimaan@gmail.com
authors.forename: Mansi
authors.initials: M
authors.lastname: Prakash
authors.forename: Manish
authors.initials: M
authors.lastname: Bodas
authors.forename: Divya
authors.initials: D
authors.lastname: Prakash
authors.forename: Neelu
authors.initials: N
authors.lastname: Nawani
authors.forename: Madhukar
authors.initials: M
authors.lastname: Khetmalas
authors.forename: Abul
authors.initials: A
authors.lastname: Mandal
authors.forename: Cecilia
authors.initials: C
authors.lastname: Eriksson
mesh_terms: D054392:Adipokines / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D037102:Lectins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D018836:Inflammation Mediators; D037102:Lectins