Anti-metastatic outcome of isoform-specific prolactin receptor targeting in breast cancer.
|
| Abstract |
Controversy exists concerning the role of the long prolactin receptor (PRLR) in the progression of breast cancer. By targeting pre-mRNA splicing, we succeeded in knocking down only the long PRLR in vivo, leaving the short forms unaffected. Using two orthotopic and highly-metastatic models of breast cancer, one of which was syngeneic (mouse 4T1) to allow assessment of tumor-immune interactions and one of which was endocrinologically humanized (human BT-474) to activate human PRLRs, we examined the effect of long PRLR knockdown on disease progression. In both models, knockdown dramatically inhibited metastatic spread to the lungs and liver and resulted in increased central death in the primary tumor. In the syngeneic model, immune infiltrates in metastatic sites were changed from innate inflammatory cells to lymphocytes, with an increase in the incidence of tumor-specific cytotoxic T cells. Long PRLR knockdown in three-dimensional culture induced apoptosis of tumor-initiating/cancer stem cells (death of 95% of cells displaying stem cell markers in 15 days). We conclude that the long PRLR plays an important role in breast cancer metastasis.
|
|---|---|
| Authors | Tomohiro Yonezawa, Kuan-Hui Ethan Chen, Mrinal K Ghosh, Lorena Rivera, Riva Dill, Lisa Ma, Pedro A Villa, Mitsumori Kawaminami, Ameae M Walker |
| Journal | Cancer letters (Cancer Lett) Vol. 366 Issue 1 Pg. 84-92 (Sep 28 2015) ISSN: 1872-7980 [Electronic] Ireland |
| PMID | 26095602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!