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; Nam Hoon Cho

doi:10.1016/j.canlet.2013.05.011

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, Nam Hoon Cho

Department of Pathology

Research output: Contribution to journal › Article › peer-review

32 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 language	English
Pages (from-to)	240-246
Number of pages	7
Journal	Cancer Letters
Volume	336
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2013.05.011
Publication status	Published - 2013 Aug 9

Bibliographical note

Funding 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

Oncology
Cancer Research

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10.1016/j.canlet.2013.05.011

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

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.",

author = "Gao, {Ming Qing} and Kim, {Baek Gil} and Suki Kang and Choi, {Yoon Pyo} and Yoon, {Joo Heon} and Cho, {Nam Hoon}",

note = "Funding 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. ",

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doi = "10.1016/j.canlet.2013.05.011",

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T1 - Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17

AU - Gao, Ming Qing

AU - Kim, Baek Gil

AU - Kang, Suki

AU - Choi, Yoon Pyo

AU - Yoon, Joo Heon

AU - Cho, Nam Hoon

N1 - Funding 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.

PY - 2013/8/9

Y1 - 2013/8/9

N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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