Abstract 1867: Enrichment of CD44high stem-cell-like cells as a possible mechanism of progestin-dependent progression of human breast cancer

Combined hormone replacement therapy (HRT) containing progestins (P) and estrogens (E) has been shown to increase the risk of breast cancer in post-menopausal women (JNCI, 2000, 92:328). We showed that the commonly used P, medroxyprogesterone acetate (MPA), increases production of the potent angiogenic growth factor VEGF in breast cancer cells (Int J Cancer, 2001, 92:469). Furthermore, it has been established that P drives tumor progression in an in-vivo xenograft model (Can Res 2007; 67:9929). CD44 has recently been shown to be expressed by cancer stem cells (CSC) (Nature Reviews Cancer 2011; 11:254), and has therefore been used as a marker for detecting and enriching of tumor initiating cells. CD44 binds potent growth factors such as VEGF and acts as a co-receptor that helps mediate proliferative and migratory signaling for a variety of receptor tyrosine kinases. Thus, we hypothesized that MPA increases CD44 levels in breast cancer cells and promotes the emergence of self-renewing stem-cell-like-cells, which support MPA-accelerated tumors in vivo. Human T47-D human breast cancer cells were treated with MPA for 24h. Subsequent FACS analysis showed that MPA caused a significant increase in CD44 protein; CD44 was induced 10-fold (Control 5.9%, MPA 60.7%). A less robust, but significant increase also occurred in BT474 cells (Control 4.0%, MPA 11.2%). Further studies showed that MPA-induced CD44high cells also had high levels of ALDH enzyme activity, a characteristic of stem cel...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Endocrinology Source Type: research