We demonstrate here increased expression of ADAM17 protein in cancer-associated fibroblasts (CAFs) extracted from human breast carcinomas compared with donor-matched normal fibroblasts, and TGF-α secretion positively correlates with ADAM17 expression in these cells. In SK-BR-3 cells co-cultured with CAFs, CAF-secreted TGF-α promotes cell proliferation by activation of EGFR, Akt, and ERK, but it does not promote cell migration. Furthermore, anti-TGF-α neutralizing antibodies antagonize the CAF-dependent increase in proliferation and activation of EGFR, Akt and ERK. Thus, pharmacologic inhibition of ADAM17 and TGF-α may have therapeutic potential for the treatment of breast cancer when fibroblast-directed therapy is considered.
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (MEST) (No. 2012R1A2A4A01006435; CNH) and by the Mid-career Researcher Program through an NRF Grant from the MEST (No. 2012R1A2A4A01006435; CNH). Preparation of the manuscript was done with the assistance of BioScience Writers LLC, Houston, TX, USA.
All Science Journal Classification (ASJC) codes
- Cancer Research