Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis.
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.


CONCLUSIONS
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.
Le
Thuc T
TT
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. thuc@purdue.edu
Huff
Terry B
TB
Cheng
Ji-Xin
JX
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D016764:Cell Polarity; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy / Q000379:methods*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000473:pathology; D013059:Spectrum Analysis, Raman / Q000379:methods*
D005227:Fatty Acids; D008055:Lipids