Cancer cell‐derived lymphotoxin mediates reciprocal tumour–stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts

Tat‐San Lau; Tony Kwok‐Hung Chung; Tak‐Hong Cheung; Loucia Kit‐Ying Chan; Leonard Wing‐Hong Cheung; So‐Fan Yim; Nelson Shing‐Shun Siu; Kwok‐Wai Lo; May Mei‐Yung Yu; Hagen Kulbe; Frances R Balkwill; Joseph Kwong

doi:10.1002/path.4258

journal article Dec 06, 2013

Cancer cell‐derived lymphotoxin mediates reciprocal tumour–stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts

Tat‐San Lau Tony Kwok‐Hung Chung Tak‐Hong Cheung Loucia Kit‐Ying Chan Leonard Wing‐Hong Cheung So‐Fan Yim Nelson Shing‐Shun Siu Kwok‐Wai Lo May Mei‐Yung Yu Hagen Kulbe Frances R Balkwill Joseph Kwong

The Journal of Pathology Vol. 232 No. 1 pp. 43-56 · Wiley

View at Publisher Save 10.1002/path.4258

Abstract

AbstractWe have investigated the role of cytokine lymphotoxin in tumour–stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin‐beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer‐associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin‐responsive cells. On the other hand, our co‐culture studies demonstrated that the cancer cell‐derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR–NF‐κB signalling. Amongst the chemokines being produced, we found that fibroblast‐secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer‐cell‐derived lymphotoxin mediates reciprocal tumour–stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin–LTBR and CXCL11–CXCR3 signalling represent therapeutic targets in ovarian cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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References

Details

Published: Dec 06, 2013
Vol/Issue: 232(1)
Pages: 43-56
License: View

Authors

T

Tat‐San Lau

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

T

Tony Kwok‐Hung Chung

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

T

Tak‐Hong Cheung

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

L

Loucia Kit‐Ying Chan

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

L

Leonard Wing‐Hong Cheung

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

S

So‐Fan Yim

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

N

Nelson Shing‐Shun Siu

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

K

Kwok‐Wai Lo

Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong Hong Kong, China

M

May Mei‐Yung Yu

Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong Hong Kong, China

H

Hagen Kulbe

Centre of Cancer and Inflammation Barts Cancer Institute, Queen Mary University of London London UK

F

Frances R Balkwill

Centre of Cancer and Inflammation Barts Cancer Institute, Queen Mary University of London London UK

J

Joseph Kwong

Department of Obstetrics and Gynaecology The Chinese University of Hong Kong Hong Kong, China

Cite This Article

Tat‐San Lau, Tony Kwok‐Hung Chung, Tak‐Hong Cheung, et al. (2013). Cancer cell‐derived lymphotoxin mediates reciprocal tumour–stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. The Journal of Pathology, 232(1), 43-56. https://doi.org/10.1002/path.4258

Cancer cell‐derived lymphotoxin mediates reciprocal tumour–stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts

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