Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17

Ming Qing Gao, Baek Gil Kim, Suki Kang, Yoon Pyo Choi, Joo Heon Yoon, Namhoon Cho

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)240-246
Number of pages7
JournalCancer Letters
Volume336
Issue number1
DOIs
Publication statusPublished - 2013 Aug 9

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Cell Proliferation
Breast Neoplasms
Neoplasms
Fibroblasts
Neutralizing Antibodies
Cell Movement
Cultured Cells
Cancer-Associated Fibroblasts
ADAM17 Protein
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Gao, Ming Qing ; Kim, Baek Gil ; Kang, Suki ; Choi, Yoon Pyo ; Yoon, Joo Heon ; Cho, Namhoon. / Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17. In: Cancer Letters. 2013 ; Vol. 336, No. 1. pp. 240-246.
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Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17. / Gao, Ming Qing; Kim, Baek Gil; Kang, Suki; Choi, Yoon Pyo; Yoon, Joo Heon; Cho, Namhoon.

In: Cancer Letters, Vol. 336, No. 1, 09.08.2013, p. 240-246.

Research output: Contribution to journalArticle

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AB - 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.

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