Inhibition of Interleukin-4, a Survival Factor for Breast Cancer Cells, as an Antimetastatic Approach
Abstract
The goal of the project is to determine the effects on metastasis of deleting or inhibiting the receptor for interleulin-4 from breast tumor cells. We proposed three aims: [1] Establish and characterize mammary tumor lines with the receptor for IL4 knocked down. [2] Determine the in vivo growth characteristics of IL4R-knockdown cells using spontaneous and experimental metastasis models; [3] Determine the therapeutic efficacy of systemic IL4 neutralizing antibody in combination with chemotherapy in a spontaneously-metastasizing breast cancer model. We have successfully achieved aim 1 for 1 of the 2 cell lines originally proposed and are continuing our efforts with the second cell line. In vitro assays have indicated that IL4 receptor indeed functions to promote proliferation and survival of the mouse mammary tumor cell line, 4T1. Further, signaling through IL4R appears to promote survival after exposure to paclitaxel. We anticipate that the in vivo assays, which are just beginning, will confirm this role of IL4R. If confirmed, then we would propose that IL4R blockade be used clinically in combination with chemotherapy to reduce the occurrence of relapse.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA542731
Entities
People
- Barbara Mary Fingleton
Organizations
- Vanderbilt University