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Adipose tissue in breast cancer: not an idle bystander but an active participant in breast cancer progression

Lore Lapeire UGent, An Hendrix UGent, Kathleen Lambein UGent, Geert Braems UGent, P Valet, Rudy Van den Broecke UGent, Marc Bracke UGent, Veronique Cocquyt UGent, Hannelore Denys UGent and Olivier De Wever UGent (2011) San Antonio Breast Cancer Symposium, 34th Annual, Abstracts.
abstract
Background: Adipose tissue is a dynamic organ that secretes a plethora of molecules called adipokines. In breast cancer we find a unique situation were genetically changed cells (the cancer cells) are in close contact with adipocytes. Moreover, obesity is a known negative prognostic marker for postmenopausal breast cancer patients. We hypothesize that adipocyte-derived factors influence breast cancer progression. Materials and methods: Adipose tissue was collected from breast cancer patients undergoing a mastectomy. After macroscopic removal of blood vessels and connective tissue, the adipose tissue was carefully cut into 2-3mm3 pieces and were incubated in specific adipose-tissue culture medium. After 24h, the medium was collected and the quality was checked by determining the concentration of total proteins, leptin, adiponectin, TNFalpha and triglycerides. This conditioned medium of adipose tissue (CM AT) was used for in vitro experimentation with MCF-7 breast cancer cells. Results: Effect of AT on morphology and aggregation: when MCF-7 cells are grown in a culture flask, they tend to form round compact islands. Under influence of CM AT, the islands form sharp edges, the cells in an island can be counted individually and they show scattering. Importantly, despite the major changes in cellular morphology, CM AT removal rescued the compact island formation of MCF-7 cells. In the slow aggregation assay, cells treated with CM AT (and a subtherapeutic concentration of a neutralizing E-cadherin antibody) lost the ability to form compact aggregates. Furthermore, MCF-7 spheroids placed inside adipose tissue showed massive reorganization into an irregularly shaped mass. Effect of AT on proliferation: starting from an equal number of cells and counting them every 2 days, it became clear that MCF-7 cells with CM AT had a higher rate of proliferation than MCF-7 cells in control medium. This stimulation of proliferation was confirmed by cell cycle analysis which revealed a doubling of cells in the G2/M phase, and western blot which showed an upregulation of cyclin A and cyclin E, both positive regulators of the cell cycle. Effect of AT on invasion: a 24h collagen type I invasion assay revealed invasive characteristics of MCF-7 cells treated with CM AT while MCF-7 cells in control conditions are round and non-invasive. In contrast, a transwell collagen test over 14 days was not able to show MCF-7 cells invading the collagen gel under influence of CM AT. However, the growth pattern of MCF-7 cells on the collagen gel was clearly disorganised when compared with the control situation. Conclusion: These findings suggest that adipose tissue-derived factors exert a dramatic selective force on patterning, invasion and growth of MCF-7 breast cancer cells. Unraveling the mechanism behind these observations may provide vital information regarding the link between obesity and poor prognosis in postmenopausal breast cancer.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
keyword
breast cancer, obesity, adipokines, adipose tissue
in
San Antonio Breast Cancer Symposium, 34th Annual, Abstracts
conference name
34th Annual San Antonio Breast Cancer Symposium (SABCS 2011)
conference location
San Antonio, TX, USA
conference start
2011-12-06
conference end
2011-12-10
language
English
UGent publication?
yes
classification
C3
additional info
uploaded document is poster version
copyright statement
I have retained and own the full copyright for this publication
id
3008916
handle
http://hdl.handle.net/1854/LU-3008916
date created
2012-10-08 15:43:15
date last changed
2012-10-11 10:36:22
@inproceedings{3008916,
  abstract     = {Background: Adipose tissue is a dynamic organ that secretes a plethora of molecules called adipokines. In breast cancer we find a unique situation were genetically changed cells (the cancer cells) are in close contact with adipocytes. Moreover, obesity is a known negative prognostic marker for postmenopausal breast cancer patients. We hypothesize that adipocyte-derived factors influence breast cancer progression. 
Materials and methods: Adipose tissue was collected from breast cancer patients undergoing a mastectomy. After macroscopic removal of blood vessels and connective tissue, the adipose tissue was carefully cut into 2-3mm3 pieces and were incubated in specific adipose-tissue culture medium. After 24h, the medium was collected and the quality was checked by determining the concentration of total proteins, leptin, adiponectin, TNFalpha and triglycerides. This conditioned medium of adipose tissue (CM AT) was used for in vitro experimentation with MCF-7 breast cancer cells.  
Results: Effect of AT on morphology and aggregation: when MCF-7 cells are grown in a culture flask, they tend to form round compact islands. Under influence of CM AT, the islands form sharp edges, the cells in an island can be counted individually and they show scattering. Importantly, despite the major changes in cellular morphology, CM AT  removal rescued the compact island formation of MCF-7 cells. In the slow aggregation assay, cells treated with CM AT (and a subtherapeutic concentration of a neutralizing E-cadherin antibody) lost the ability to form compact aggregates. Furthermore, MCF-7 spheroids placed inside adipose tissue showed massive reorganization into an irregularly shaped mass.
Effect of AT on proliferation: starting from an equal number of cells and counting them every 2 days, it became clear that MCF-7 cells with CM AT had a higher rate of proliferation than MCF-7 cells in control medium. This stimulation of proliferation was confirmed by cell cycle analysis which revealed a doubling of cells in the G2/M phase, and western blot which showed an upregulation of cyclin A and cyclin E, both positive regulators of the cell cycle. 
Effect of AT on invasion: a 24h collagen type I invasion assay revealed invasive characteristics of MCF-7 cells treated with CM AT while MCF-7 cells in control conditions are round and non-invasive. In contrast, a transwell collagen test over 14 days was not able to show MCF-7 cells invading the collagen gel under influence of CM AT. However, the growth pattern of MCF-7 cells on the collagen gel was clearly disorganised when compared with the control situation.  
Conclusion: These findings suggest that adipose tissue-derived factors exert a dramatic selective force on patterning, invasion and growth of MCF-7 breast cancer cells. Unraveling the mechanism behind these observations may provide vital information regarding the link between obesity and poor prognosis in postmenopausal breast cancer.},
  author       = {Lapeire, Lore and Hendrix, An and Lambein, Kathleen and Braems, Geert and Valet, P and Van den Broecke, Rudy and Bracke, Marc and Cocquyt, Veronique and Denys, Hannelore and De Wever, Olivier},
  booktitle    = {San Antonio Breast Cancer Symposium, 34th Annual, Abstracts},
  keyword      = {breast cancer,obesity,adipokines,adipose tissue},
  language     = {eng},
  location     = {San Antonio, TX, USA},
  title        = {Adipose tissue in breast cancer: not an idle bystander but an active participant in breast cancer progression},
  year         = {2011},
}

Chicago
Lapeire, Lore, An Hendrix, Kathleen Lambein, Geert Braems, P Valet, Rudy Van den Broecke, Marc Bracke, Veronique Cocquyt, Hannelore Denys, and Olivier De Wever. 2011. “Adipose Tissue in Breast Cancer: Not an Idle Bystander but an Active Participant in Breast Cancer Progression.” In San Antonio Breast Cancer Symposium, 34th Annual, Abstracts.
APA
Lapeire, Lore, Hendrix, A., Lambein, K., Braems, G., Valet, P., Van den Broecke, R., Bracke, M., et al. (2011). Adipose tissue in breast cancer: not an idle bystander but an active participant in breast cancer progression. San Antonio Breast Cancer Symposium, 34th Annual, Abstracts. Presented at the 34th Annual San Antonio Breast Cancer Symposium (SABCS 2011).
Vancouver
1.
Lapeire L, Hendrix A, Lambein K, Braems G, Valet P, Van den Broecke R, et al. Adipose tissue in breast cancer: not an idle bystander but an active participant in breast cancer progression. San Antonio Breast Cancer Symposium, 34th Annual, Abstracts. 2011.
MLA
Lapeire, Lore, An Hendrix, Kathleen Lambein, et al. “Adipose Tissue in Breast Cancer: Not an Idle Bystander but an Active Participant in Breast Cancer Progression.” San Antonio Breast Cancer Symposium, 34th Annual, Abstracts. 2011. Print.