Accession Number:

ADA454757

Title:

Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

Descriptive Note:

Final rept.

Corporate Author:

INSTITUTE FOR CLINICAL RESEARCH INC WASHINGTON DC

Personal Author(s):

Report Date:

2005-10-01

Pagination or Media Count:

12.0

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 BALBc 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 F48O 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.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE