Notch3 as a Tumor Suppressor in the Postpartum Mammary Gland
Abstract
We recently reported a tumor-suppressive function for Notch3 in the parous mammary gland through the restriction of parity-identified mammary epithelial cell (PI-MEC) expansion. Unexpectedly, syngeneic transplantation experiments revealed that the post-lactational involuting mammary microenvironment of Notch3 knockout (Notch3-/-) mice suppressed tumor growth compared to that of wildtype mice. Moreover, non-parous mammary microenvironment of Notch3-/- mice also exhibited anti-tumor activity, and the tumor-suppressive effect was observed even when breast cancer cells were ectopically transplanted to a posterior dorsolateral site. To test whether suppression of tumor growth in Notch3-/- hosts is mediated through immune cells, we performed co-culture of breast cancer cells with splenocytes isolated from mice following tumor cell inoculation. Indeed, splenocytes from Notch3-/-, but not wildtype, mice showed potent cytotoxicity against cancer cells. Thus, contrary to its tumor-suppressive function in the postpartum mammary epithelium, Notch3 may facilitate tumor development through the repression of anti-tumor immunity in tumor microenvironment. We are currently studying the mechanisms underlying the Notch3 modulation of anti-tumor immunity.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1199737
Entities
People
- Keli Xu
Organizations
- University of Mississippi Medical Center