Back to Search
Start Over
PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts
- Source :
- Experimental and Molecular Pathology. 100:17-25
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- In this paper, we aimed to explore whether progranulin (PGRN) could induce epithelial ovarian cancer cells to undergo an epithelial mesenchymal transition (EMT) program directly and through its activation of cancer associated fibroblasts (CAFs) indirectly. Immunohistochemistry(IHC) staining of tissue samples of 78 cases of epithelial ovarian cancer (EOC) patients found that PGRN expression levels were negatively correlated with E-cadherin levels (r=-0.289, P=0.013) and positively correlated with Slug levels (r=0.332, P=0.003); Cell experiments showed that PGRN overexpression could increase the migratory and invasive abilities of A2780 cells significantly. Moreover, high doses (62ng/ml) of recombinant PGRN could induce 14.7 fold high expression of smooth muscle actin α (α-SMA) in human normal fibroblasts. In addition, patients with both high levels of PGRN and α-SMA in their tissue samples had the worst disease free survival (DFS) and overall survival (OS) than those with low levels of PGRN or α-SMA. All the results suggest that PGRN could promote invasiveness of EOC cells through an EMT program directly and through activation of CAFs indirectly. This may provide a new effective therapy target for EOC.
- Subjects :
- Adult
0301 basic medicine
Pathology
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Clinical Biochemistry
Cell
Carcinoma, Ovarian Epithelial
Biology
Pathology and Forensic Medicine
Metastasis
03 medical and health sciences
Progranulins
0302 clinical medicine
Cell Movement
Tumor Microenvironment
medicine
Humans
Neoplasm Invasiveness
Neoplasms, Glandular and Epithelial
Epithelial–mesenchymal transition
Molecular Biology
Cell Proliferation
Ovarian Neoplasms
Tumor microenvironment
Cadherin
Cell growth
Fibroblasts
Middle Aged
Cadherins
medicine.disease
Coculture Techniques
030104 developmental biology
medicine.anatomical_structure
Lymphatic Metastasis
030220 oncology & carcinogenesis
Cancer research
Intercellular Signaling Peptides and Proteins
Immunohistochemistry
Cancer-Associated Fibroblasts
Female
Subjects
Details
- ISSN :
- 00144800
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Experimental and Molecular Pathology
- Accession number :
- edsair.doi.dedup.....ded3deca47a15e5f658476e157f9a227