title: Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis.
abstract: Cancer cells typically demonstrate altered morphology during the various stages of disease progression as well as metastasis. While much is known about how altered cell morphology in cancer is a result of genetic regulation, less is known about how changes in cell morphology affect cell function by influencing gene expression. In this study, we altered cell morphology in different types of cancer cells by disrupting the actin cytoskeleton or by modulating attachment and observed a rapid up-regulation of growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta (TGF-β) super-family. Strikingly, this up-regulation was sustained as long as the cell morphology remained altered but was reversed upon allowing cell morphology to return to its typical configuration. The potential significance of these findings was examined in vivo using a mouse model: a small number of cancer cells grown in diffusion chambers that altered morphology increased mouse serum GDF15. Taken together, we propose that during the process of metastasis, cancer cells experience changes in cell morphology, resulting in the increased production and secretion of GDF15 into the surrounding environment. This indicates a possible relationship between serum GDF15 levels and circulating tumor cells may exist. Further investigation into the exact nature of this relationship is warranted.
authors.affiliation: The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Koh Meng
authors.initials: KM
authors.lastname: Aw Yong
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.forename: Donald
authors.initials: D
authors.lastname: Vindivich
authors.forename: Jude M
authors.initials: JM
authors.lastname: Phillip
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Wu
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.forename: Robert H
authors.initials: RH
authors.lastname: Getzenberg
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape; D047630:Depsipeptides / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D013997:Time Factors; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger; D053778:Thiazolidines; C057531:jasplakinolide; C037068:latrunculin B