|
Abstract:
The presence of some innate immune cell types in developing neoplasms provides a significant pro-tumor advantage. Myeloidlineage immune cells, such as tumor-associated macrophages (TAMs) and immature myeloid-derived cells/monocytes, promote tumor development by exerting pro-tumor activities including activating angiogenic programs, suppressing anti-tumor immunity, and enhancing migratory and metastatic properties of malignant cells. Cathepsin C (CTSC) is a lysosomal cysteineclass hydrolase expressed in most mammalian tissues. In myeloid cells and cytotoxic lymphocytes, CTSC regulates catalytic activation of several important leukocyte-derived serine proteases including granzymes, chymases and elastases. Preliminary data from the Coussens? laboratory has revealed that in a mouse model of de novo mammary adenocarcinoma development, neither latency of progression to primary tumors, tumor burden, nor tumor histopathology is regulated by CSTC; however, in cathepsin C (Ctsc)-deficient mice, there is a significant reduction in the number of circulating malignant cells in peripheral blood, with a corresponding significant reduction in pulmonary metastasis development, thus indicating that CC plays a predominant role in metastatic dissemination of primary mammary tumors. Since CTSC expression in mammary adenocarcinomas is largely localized in TAMs, these provocative data indicate that macrophages play an important role in regulating intravasation and/or survival of malignant cells in peripheral blood, and that this function is at least partly dependent on CTSC.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary 1 Sep 2009-31 Aug 2010 |
| Pages: |
25 |
| Report Date: |
SEP 2010 |
| Contract Number: |
W81XWH-09-1-0543 |
| Report Number: |
A529435 |
|
|
|
|
|
Keywords relating to this report:
Email This Abstract
