Characterization of HCT116 human colon cancer cells in an orthotopic model.
BACKGROUND
Colorectal cancer metastases result in a significant number of cancer related deaths. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. In the absence of any transgenic models of colon cancer metastases, an in vivo model system that fulfills the rate limiting steps of metastasis (local invasion and distant colony formation) is needed. The purpose of this study was to characterize the behavior of a human colon cancer cell line, HCT116 in an orthotopic model.


METHODS
HCT116 cells were transfected with green fluorescence protein and subcutaneously injected into BALB/c nude male mice. Once xenografts were established, they were excised and orthotopically implanted into 32 other male BALB/c nude mice using microsurgical techniques. Animals were serially imaged and euthanized at 6-8 weeks post-implantation. Tissues were procured and processed for hematoxylin and eosin analysis.


RESULTS
All 32 animals demonstrated primary tumor growth, invasion and peritoneal spread. Liver metastases were identified in 15/32 (47%), and lung metastases were confirmed in 13/32 (41%). In total, 19/32 (59%) animals demonstrated distant metastatic colony formation.


CONCLUSIONS
This orthotopic model of colon cancer fulfills the rate limiting steps of local invasion and distant colony formation in the process of metastases. HCT116 human colon cancer cell line in this in vivo model system provides a tool to dissect the molecular mechanism involved in the metastatic cascade.
Rajput
Ashwani
A
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. ashwani.rajput@roswellpark.org
Dominguez San Martin
Ivan
I
Rose
Rebecca
R
Beko
Alexander
A
Levea
Charles
C
Sharratt
Elizabeth
E
Mazurchuk
Richard
R
Hoffman
Robert M
RM
Brattain
Michael G
MG
Wang
Jing
J
D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D045325:HCT116 Cells / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental