Kallikrein-related peptidase 7 promotes multicellular aggregation via the α5β1 integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma

Dong, Ying, Tan, Olivia L., Loessner, Daniela, Stephens, Carson, Walpole, Carina, Boyle, Glen M., Parsons, Peter G. and Clements, Judith A. (2010) Kallikrein-related peptidase 7 promotes multicellular aggregation via the α5β1 integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma. Cancer Research, 70 7: 2624-2633. doi:10.1158/0008-5472.CAN-09-3415


Author Dong, Ying
Tan, Olivia L.
Loessner, Daniela
Stephens, Carson
Walpole, Carina
Boyle, Glen M.
Parsons, Peter G.
Clements, Judith A.
Title Kallikrein-related peptidase 7 promotes multicellular aggregation via the α5β1 integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma
Formatted title
Kallikrein-related peptidase 7 promotes multicellular aggregation via the α5β1 integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2010-04-01
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-09-3415
Volume 70
Issue 7
Start page 2624
End page 2633
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2011
Language eng
Formatted abstract
Kallikrein-related peptidase 7 (KLK7) is upregulated in epithelial ovarian carcinoma (EOC) with high levels correlated with poor prognosis. However, the mechanisms underlying this relationship and the role of KLK7 in EOC progression are unknown. We report that two different KLK7 transcripts, KLK7-253 and KLK7-181, are simultaneously expressed in high-grade serous EOC. Multicellular aggregates (MCA), which promote cell survival and chemoresistance, were observed in SKOV-3 cells stably overexpressing KLK7-253 in particular. Importantly, these MCAs invade into a monolayer of mesothelial cells and form cancer cell focL Blocking MCA using antibodies against KLK7 and α5β 1, and β1 integrins confirmed the involvement of KLK7 and integrinregulated cell adhesion. Increased levels of α5/ β1 integrins and enhanced attachment to fibronectin and vitronectin, which was blocked with an anti-β1 integrin antibody, were also observed. Finally, Western blot and immunohistochemistry showed higher KLK7 and α5/β:1 integrin levels in serous EOC cells from ascites and tumor samples from chemotherapy nonresponders with short postsurvival times. Additionally, both KLK7253 and KLK7-181 clones were more resistant to paclitaxel treatment in vitro. These findings suggest a mechanism for the association of high KLK7 levels with chemoresistance and poor prognosis for serous EOC patients by promotion of peritoneal dissemination and reinvasion via increased MCA and α5β1, integrin-dependent cell adhesion. © 2010 American Association for Cancer Research.
Keyword Animals
Cell aggregation
Cell line
Tumor
Cystadenocarcinoma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
ERA 2012 Admin Only
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Created: Wed, 30 Mar 2011, 11:45:45 EST by Lisa Hennell on behalf of School of Medicine