Mammal with an orthotopic tumor capable of metastasis, a method of making and a method of using
Provided are compositions and methods that involve cancer cells which are modified so that they can form orthotopic tumors in a non-human mammal, and wherein metastasis of the tumor can be controlled. The cancer cells, which may be human cancer cells, are modified so that expression of a human chemokine receptor can be modulated. Modulating expression of the human chemokine receptor allows selective initiation of metastasis. Kits which contain the modified cancer cells are provided. A method for identifying agents which can inhibit metastasis using non-human mammals having orthotopic tumors formed using the modified cancer cells is also included.
1. A method for making a non-human mammal comprising an orthotopic tumor in its gastrointestinal tract that metastasizes to the lungs and/or liver comprising:
a) introducing into a non-human mammal a plurality of human Chemokine Receptor 9 positive (CCR9+) colorectal cancer cells, wherein subsequent to the introduction the human colorectal cancer cells form a tumor in the gastrointestinal tract of the non-human mammal, wherein the cancer cells contain an expression vector, wherein the expression vector comprises an inducible promoter that controls expression of an shRNA targeted to the human CCR9, the method further comprising inducing the expression of the shRNA such that the tumor metastasizes to the lungs and/or liver.
2. A non-human mammal comprising an orthotopic a tumor in its gastrointestinal tract that metastasizes to the lungs and/or liver made by the method of claim 1 .
3. A method for determining whether a test agent is a candidate for inhibition of metastasis comprising providing a non-human animal of claim 2 , allowing metastasis of the orthotopic tumor to the lungs and/or liver, and after a period of time measuring metastasis of the tumor to the lungs and/or liver, wherein a reduction of metastasis relative to a control indicates that the test agent is a candidate for use as an inhibitor of metastasis of the tumor to the lungs and/or liver.