Date of Award

1-1-2013

Document Type

Open Access Dissertation

Department

Biological Sciences

First Advisor

Franklin G Berger

Second Advisor

Maria Marjorette O Peña

Abstract

Colon cancer is the third most frequent cancer and the second leading cause of cancer deaths in the United States. Liver metastasis is the major cause of death in colon cancer. Successful metastases depend on productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, target organ environments, and cells in the hematopoietic compartment.

To identify the host-tumor interactions promoting liver metastasis and their molecular and cellular mediators, an orthotopic mouse model of liver metastasis of colon cancer was established that recapitulates all stages of tumor growth and metastasis. A highly metastatic mouse carcinoma cell line CT26-FL3 was isolated from the CT26 colon adenocarcinoma cell line by in vivo selection. The CT26-FL3 cells were found to be more proficient in inducing a metastasis-promoting host environment as compared to the parental cell line. Using this mouse model, microarray analyses were utilized to determine the genetic signature of the highly metastatic CT26-FL3 cells and the genetic changes in the liver microenvironment in mice bearing tumors from CT26-FL3 cells before and during metastasis. The results showed CT26-FL3 induced immune responses and released numerous cytokines. Furthermore, Il33 and Lcn2 were selected from the genetic signature of cancer cells and liver environment respectively as target genes to verify their roles in promoting liver metastasis of colorectal cancer.

Rights

© 2013, Yu Zhang

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