title: PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts.
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.
authors.affiliation: Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China; School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Programs of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250017, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China. Electronic address: stevendtt@163.com.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, PR China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250017, PR China. Electronic address: wanglinlinatjn@163.com.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D015820:Cadherins / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D000077153:Progranulins; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D015820:Cadherins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Cancer associated fibroblasts; Epithelial mesenchymal transition; Epithelial ovarian cancer; Metastasis; PGRN