Author:
Le Thuc T,Huff Terry B,Cheng Ji-Xin
Abstract
Abstract
Background
Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development.
Methods
Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments.
Results
CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells.
Conclusion
Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference35 articles.
1. Rose DP, Connolly JM, Meschter CL: Effect of Dietary-Fat on Human Breast-Cancer Growth and Lung Metastasis in Nude-Mice. J Natl Cancer Inst. 1991, 83 (20): 1491-1495. 10.1093/jnci/83.20.1491.
2. Calle EE, Kaaks R: Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004, 4 (8): 579-591. 10.1038/nrc1408.
3. World Cancer Research Fund/American Institute for Cancer Research: Food, nutrition, physical activity, and the prevention of cancer: a global perspective. 2007, Washington DC: AICR
4. Thiebaut ACM, Schatzkin A, Ballard-Barbash R, Kipnis V: Dietary fat and breast cancer: Contributions from a survival trial. J Natl Cancer Inst. 2006, 98 (24): 1753-1755.
5. Fontham ETH: Diet and lung cancer. Cancer Causes & Control. 1997, 8 (6): 819-820. 10.1023/A:1018432916540.
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