title: A highly metastatic Lewis lung carcinoma orthotopic green fluorescent protein model.
abstract: The Lewis lung carcinoma has been widely used for many important studies. However, the subcutaneous transplant or orthotopic cell-suspension injection models have not allowed the expression of its full metastatic potential. A powerful new highly metastatic model of the widely-used Lewis lung carcinoma is reported here using surgical orthotopic implantation (SOI) of tumor fragments and enhanced green fluorescent protein (GFP) transduction of the tumor cells. To achieve this goal, we first developed in vitro a stable high-expression GFP transductant of the Lewis lung carcinoma with the pLEIN retroviral expression vector containing the enhanced Aequorea victoria GFP gene. Stable high-level expression of GFP was found maintained in vivo in subcutaneously-growing Lewis lung tumors. The in vivo GFP-expressing tumors were harvested and implanted as tissue fragments by SOI in the right lung of additional nude mice. This model resulted in rapid orthotopic growth and extensive metastasis visualized by GFP-expression. 100% of the animals had metastases on the ipsilateral diaphragmatic surface, contralateral diaphragmatic surface, contralateral lung parenchima, and in mediastinal lymph nodes. Heart metastases were visualized in 40%, and brain metastases were visualized in 30% of the SOI animals. Mice developed signs of respiratory distress between 10-15 days post-tumor implantation and were sacrificed. The use of GFP-transduced Lewis lung carcinoma transplanted by SOI reveals for the first time the high malignancy of this tumor and provides an important useful model for metastasis, angiogenesis and therapeutic studies.
authors.affiliation: AntiCancer, Inc., San Diego, California 92111, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rashidi
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Jiang
authors.forename: E
authors.initials: E
authors.lastname: Baranov
authors.forename: Z
authors.initials: Z
authors.lastname: An
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: A R
authors.initials: AR
authors.lastname: Moossa
authors.forename: R M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins