Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy
Abstract
Tumor-associated macrophages may comprise up to 50% of the tumor mass in breast cancer and are capable of producing estrogen and angiogenic cytokines that regulate the growth and angiogenesis of breast cancer. The purpose of this study is to determine whether intratumoral injecUon of liposome-encapsulated dichlornmethyene diphosphonate (clodronate). a potent macrophage-depleting agent. can deplete tumor-associated macrophages in a murine breast cancer model. and whether depletion of tumor-associated macrophages has any effect on the tumor growth. The breast cancer model was established in BALB/c mice by subcutaneous injection of estrogen receptor-positive murine mammary tumor cells (4T1). Two weeks after injection of 4T1 cells, tumor-bearing mice were divided into 3 groups. The first group served as control with no further injection. The second group was injected intratumorally with liposomes containing clodronate. The third group was injected with liposomes containing phosphate-buffered saline. The tumor size was measured every 2-3 days using a caliper. At 1,3,5.7 and 9 days after liposome injection, tumors were harvested, fixed. and immuno-stained with antibodies to macrophage-specific markers (F4/8O and Mac-1) to quantify the number of macrophages. The infiltrating macrophages were quantified using Chalkley Counting method with a 25-point array reticle. Results showed that the intratumoral injection of 10, 30 or 60 micronliter liposome-encapsulated clodronate had no effect on the tumor growth and tumor-associated macrophages in this murine 4T1 breast cancer model. Whether liposome-encapsulated clodronate at a higher dosage has any effect needs further investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA454757
Entities
People
- Baochong Gao
- Min-fu Tsan