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Title: Pregnancy Associated Plasma Protein-A links pregnancy and melanoma progression by promoting cellular migration and invasion.
Austin Authors: Prithviraj, Prashanth;Anaka, Matthew;McKeown, Sonja J;Permezel, Michael;Walkiewicz, Marzena;Cebon, Jonathan S ;Behren, Andreas;Jayachandran, Aparna
Affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, Australia
Cancer Immunobiology Laboratory, Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, University of Melbourne, Victoria, Australia
Mercy Hospital for Women, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Victoria, Australia
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: 10-Apr-2015
Publication information: Oncotarget 2015; 6(18): 15953-15965
Abstract: Melanoma is the most common cancer diagnosed in pregnant women and an aggressive course with poorer outcomes is commonly described during pregnancy or shortly after childbirth. The underlying mechanisms for this are not understood. Here, we report that melanoma migration, invasiveness and progression are promoted by Pregnancy-Associated Plasma Protein-A (PAPPA), a pregnancy-associated metalloproteinase produced by the placenta that increases the bioavailability of IGF1 by cleaving it from a circulating complex formed with IGFBP4. We show that PAPPA is widely expressed by metastatic melanoma tumors and is elevated in melanoma cells exhibiting mesenchymal, invasive and label-retaining phenotypes. Notably, inhibition of PAPPA significantly reduced invasion and migration of melanoma cells in vitro and in vivo within the embryonic chicken neural tube. PAPPA-enriched pregnancy serum treatment enhanced melanoma motility in vitro. Furthermore, we report that IGF1 can induce the phenotypic and functional effects of epithelial-to-mesenchymal transition (EMT) in melanoma cells. In this study, we establish a clear relationship between a pregnancy-associated protein PAPPA, melanoma and functional effects mediated through IGF1 that provides a plausible mechanism for accelerated melanoma progression during pregnancy. This opens the possibility of targeting the PAPPA/IGF1 axis therapeutically.
Gov't Doc #: 25940796
ORCID: 0000-0001-5329-280X
PubMed URL: 25940796
Type: Journal Article
Subjects: EMT
Appears in Collections:Journal articles

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