Date of Award

Spring 5-5-2017

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. Maria Marjorette Pena

First Reader

Ms. Kristen Larsen

Abstract

Lipocalin 2 (Lcn2) is a member of the lipocalin family of siderophore-binding molecules that can mediate iron trafficking. It acts during the innate immune response and has been implicated in conflicting roles in metastasis, leaving its role undefined. In breast cancer LCN2 was shown in previous studies to both inhibit or promote metastasis. Previous studies the Pena laboratory showed that increasing the serum levels of LCN2 caused a significantly increase in liver metastasis of the poorly metastatic MC-38 colon cancer cell line. In this study, we examined the ability of LCN2 to promote metastasis of colon and other cancers to the lung to determine its functionality as a multi-organ determinant of metastatic growth. The effect of elevated circulating levels of LCN2 on lung metastasis was tested on mouse models using MC-38 colon adenocarcinoma cells, 4T1 breast cancer cells, and B16-F10 melanoma cells using C57B1/6 (B6), Balb/c, and B6 mice, respectively. Isolated using endotoxin free methods, pV1J-LCN2 plasmid was utilized for in vivo electroporation of the mice, with the cancerous cells injected using tail-vein, mammary fat pad, and subcutaneous injections. The empty vector, pV1J was used as the control. Blood serum and in vivo bioluminescent images were obtained weekly, along with caliper measurements of the primary tumor. Mice were sacrificed after three weeks and the lungs, liver, and spleen were weighed and examined for metastasis post-mortem. Preliminary results indicate that LCN2 promoted a significant increase in tumor mass in all three cell lines. Though some metastasis was observed, further studies are required to determine the extent of the metastatic potential of LCN2.

First Page

1

Last Page

31

Rights

© 2017, Lauren Strzyzewski

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