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CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling

Overview of attention for article published in Molecular Cancer, September 2016
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Title
CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling
Published in
Molecular Cancer, September 2016
DOI 10.1186/s12943-016-0542-2
Pubmed ID
Authors

Denis Lane, Isabelle Matte, Claude Laplante, Perrine Garde-Granger, Alex Carignan, Paul Bessette, Claudine Rancourt, Alain Piché

Abstract

Ovarian cancer (OC) ascites consist in a proinflammatory tumor environment that is characterized by the presence of various cytokines, chemokines and growth factors. The presence of these inflammatory-related factors in ascites is associated with a more aggressive tumor phenotype. CCL18 is a member of CCL chemokines and its expression has been associated with poor prognosis in some cancers. However, its role in OC progression has not been established. Therefore, the aim of the current study was to elucidate the role of ascites CCL18 in OC progression. ELISA and tissue microarrays were used to assess CCL18 in ascites and phospho-Pyk2 expression in cancer tissues respectively. Cell migration was assessed using Boyden chambers. CCL18 and ascites signaling was examined in ovarian cancer cells utilizing siRNA and exogenous gene expression. Here, we show that CCL18 levels are markedly increased in advanced serous OC ascites relative to peritoneal effusions from women with benign conditions. Ascites and CCL18 dose-dependently enhanced the migration of OC cell lines CaOV3 and OVCAR3. CCL18 levels in ascites positively correlated with the ability of ascites to promote cell migration. CCL18 blocking antibodies significantly attenuated ascites-induced cell migration. Ascites and CCL18 stimulated the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) in CaOV3 and OVCAR3 cells. Most importantly, the expression of phosphorylated Pyk2 in serous OC tumors was associated with shorter progression-free survival. Furthermore, enforced expression of Pyk2 promoted tumor cell migration while siRNA-mediated downregulation of Pyk2 attenuated cell migration. Downregulation of Pyk2 markedly inhibited ascites and CCL18-induced cell migration. Taken together, our findings establish an important role for CCL18, as a component of ascites, in the migration of tumor cells and identify Pyk2 as prognostic factor and a critical downstream signaling pathway for ascites-induced OC cell migration.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 19%
Student > Master 6 16%
Student > Bachelor 4 11%
Other 3 8%
Student > Doctoral Student 2 5%
Other 8 22%
Unknown 7 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 24%
Medicine and Dentistry 7 19%
Nursing and Health Professions 3 8%
Veterinary Science and Veterinary Medicine 2 5%
Engineering 2 5%
Other 4 11%
Unknown 10 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 September 2016.
All research outputs
#20,340,423
of 22,886,568 outputs
Outputs from Molecular Cancer
#1,484
of 1,725 outputs
Outputs of similar age
#287,534
of 330,061 outputs
Outputs of similar age from Molecular Cancer
#10
of 10 outputs
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