search button

Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV

  • Authors:
    • Qingyu Cui
    • Bixiao Wang
    • Kaifu Li
    • Haichen Sun
    • Tao Hai
    • Yan Zhang
    • Hua Kang

  • View Affiliations

  • Published online on: July 5, 2018     https://doi.org/10.3892/ol.2018.9092
  • Pages: 3537-3544

  • Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Chemotherapy is an important comprehensive treatment for breast cancer, which targets micro‑environment of tumors as well as their characterisitcs. A previous microarray analysis revealed that matrix metalloproteinase (MMP)‑1 was highly upregulated in carcinoma-associated fibroblasts (CAFs) prior to and following treatment with Taxotere under co‑culture conditions. However, whether the chemotherapeutic effects of Taxotere were influenced by the changes in MMP‑1 remained unclear. The purpose of the present study was to investigate the impact and mechanism of CAFs in regulating the efficacy of Taxotere on breast cancer cells. CAFs isolated from primary invasive ductal human breast tumors following surgical resection, were used in co‑culture with MDA‑MB‑231 cells to simulate the tumor micro‑environment. Following the addition of Taxotere, changes in MMP‑1 gene and protein expression were assessed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Proliferation, invasion and apoptosis assays revealed that when MMP‑1 was upregulated in CAFs, the therapeutic efficacy of Taxotere was reduced in breast cancer cells. Chemosensitivity was significantly increased when MMP‑1 expression was inhibited by GM6001. In addition, Collagen IV was upregulated in CAFs following chemotherapy and protected breast cancer cells against chemotherapeutic side effects. Collagen IV expression significantly decreased, as well as MMP‑1 expression when GM6001 was added. Proliferation and invasion assays demonstrated that the exogenous addition of Collagen IV weakend the chemotherapeutic effect of Taxotere on breast tumor cells. Overall, the results revealed that in CAFs, MMP‑1 synergized with Collagen IV as a key gene in regulating the chemotherapeutic effect of Taxotere on breast tumor cells and served an important role in reducing the efficacy of Taxotere on breast cancer, potentially via the transforming growth factor‑β signaling pathway. These fidings provide a theoretical basis for the mechanism of CAFs in reducing the chemotherapeutic effect of Taxotere on breast cancer cells and a novel approach for enhancing the chemosensitivity of tumors.
View Figures
View References

Related Articles

Journal Cover

September-2018
Volume 16 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 2.5
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Cui Q, Wang B, Li K, Sun H, Hai T, Zhang Y and Kang H: Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV. Oncol Lett 16: 3537-3544, 2018.
APA
Cui, Q., Wang, B., Li, K., Sun, H., Hai, T., Zhang, Y., & Kang, H. (2018). Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV. Oncology Letters, 16, 3537-3544. https://doi.org/10.3892/ol.2018.9092
MLA
Cui, Q., Wang, B., Li, K., Sun, H., Hai, T., Zhang, Y., Kang, H."Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV". Oncology Letters 16.3 (2018): 3537-3544.
Chicago
Cui, Q., Wang, B., Li, K., Sun, H., Hai, T., Zhang, Y., Kang, H."Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV". Oncology Letters 16, no. 3 (2018): 3537-3544. https://doi.org/10.3892/ol.2018.9092