title: Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells.
abstract: Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa.
authors: Australian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Varinder
authors: V
authors: Jeet
authors: Australian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Gregor
authors: G
authors: Tevz
authors: Australian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, CanadaAustralian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Melanie
authors: M
authors: Lehman
authors: Australian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Brett
authors: B
authors: Hollier
authors: Australian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, CanadaAustralian Prostate Cancer Research Centre - QueenslandInstitute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, AustraliaDepartment of Urologic SciencesVancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada colleen.nelson@qut.edu.au.
authors: Colleen
authors: C
authors: Nelson
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D001549:Benzamides; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D000071451:Chitinase-3-Like Protein 1; D013196:Dihydrotestosterone / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D054392:Adipokines; D000726:Androgen Antagonists; D000728:Androgens; D001549:Benzamides; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D009570:Nitriles; D013196:Dihydrotestosterone; D010669:Phenylthiohydantoin; D015741:Metribolone; C540278:enzalutamide
keywords: YKL40; cell invasion; cell migration; metastasis; prostate cancer; targeted therapy