Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues.
Imaging mass cytometry was used for direct visualization of platinum localization in tissue sections from tumor and normal tissues of cisplatin-treated mice bearing pancreas cancer patient-derived xenografts. This recently-developed technology enabled simultaneous detection of multiple markers to define cell lineage, DNA damage response, cell proliferation and functional state, providing a highly detailed view of drug incorporation in tumor and normal tissues at the cellular level. A striking and unanticipated finding was the extensive binding of platinum to collagen fibers in both tumor and normal mouse tissues. Time course experiments indicated the slow release of stroma-bound platinum, although it is currently unclear if released platinum retains biological activity. Imaging mass cytometry offers a unique window into the in vivo effects of platinum compounds, and it is likely that this can be extended into the clinic in order to optimize the use of this important class of agent.
Fluidigm Canada Inc., 1380 Rodick Road, Markham, Ontario L3R 4G5, Canada.
Qing
Q
Chang
Fluidigm Canada Inc., 1380 Rodick Road, Markham, Ontario L3R 4G5, Canada.
Olga I
OI
Ornatsky
Department of Pathology, Hospital for Sick Children, 555 University Avenue, Ontario M5G 1X8, Canada.
Iram
I
Siddiqui
Fluidigm Canada Inc., 1380 Rodick Road, Markham, Ontario L3R 4G5, Canada.
Rita
R
Straus
Fluidigm Canada Inc., 1380 Rodick Road, Markham, Ontario L3R 4G5, Canada.
Vladimir I
VI
Baranov
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
David W
DW
Hedley
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002945:Cisplatin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003094:Collagen; D002945:Cisplatin