Methods and Compositions for Making Animal Models of Cancer with Controllable Metastasis

Currently available models of cancer do not recapitulate the tumor microenvironment of patients and seldom metastasize.

Cornell inventors discovered that the chemokine receptor 9 (CCR9), and its ligand chemokine 25 (CCL25), are an important signaling system in cancer formation and metastasis.

They discovered that in tumors, CCR9 receptor expression levels are highest in early stage colon adenomas and progressively decrease in invasive and metastatic colorectal cancer; systematically injected CCR9+ colon-cancer-initiating cells lead to the formation of correctly located gastrointestinal tumors; and blocking CCR9 signaling with antibodies against CCL25 or with doxycycline-inducible expression of anti-CCR9 shRNA inhibits further tumor formation and drives metastasis. The inventors used human cancer cell lines in their experiments, but mouse or rat cell lines would also work in this system, which would allow immunological and other experiments to be conducted.

This invention will be useful to other basic researchers and to companies developing cancer drugs.

Potential Applications

• Mouse models of cancer with correctly located tumors and inducible metastasis
• A method to screen drugs inhibiting metastasis
• Kits containing expression vectors to make the modified cancer cells and metastasis-inducing agents
• Kits containing cell preparations already expressing CCR9 and optionally, expressing doxycycline-inducible anti-CCR9 shRNA, along with metastasis-inducing agents