Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis

Koh Meng Aw Yong, Yu Zeng, Donald Vindivich, Jude M. Phillip, Pei Hsun Wu, Denis Wirtz, Robert H. Getzenberg

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)362-373
Number of pages12
JournalJournal of Cellular Physiology
Volume229
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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