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Theranostics 2018; 8(18):5072-5087. doi:10.7150/thno.26546 This issue Cite

Review

The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer

Qiqing Sun^1,2,3,4#, Bo Zhang^1,2,3,4#, Qiangsheng Hu^1,2,3,4, Yi Qin^1,2,3,4, Wenyan Xu^1,2,3,4, Wensheng Liu^1,2,3,4, Xianjun Yu^1,2,3,4✉, Jin Xu^1,2,3,4✉

1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
3. Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
4. Shanghai Pancreatic Cancer Institute, Shanghai 200032, China.
# These authors contributed equally to this article.

✉ Corresponding authors: Xianjun Yu, MD, PhD, Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, No. 270 DongAn Road, Shanghai, P. R. China, Postal code: 200032. Tel: +86-021-64175590 ext 1307, Fax: +86-021-64031446. E-mail: yuxianjunorg Jin Xu, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China. Tel: +86-21-64175590, Fax: +86-21-64031446. E-mail: xujinorg. More

Abstract

Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most challenging lethal tumors and has a very poor prognosis. In addition to cancer cells, the tumor microenvironment created by a repertoire of resident and recruited cells and the extracellular matrix also contribute to the acquisition of hallmarks of cancer. Among these factors, cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. CAFs originate from the activation of resident fibroblasts and pancreatic stellate cells, the differentiation of bone marrow-derived mesenchymal stem cells and epithelial-to-mesenchymal transition. CAFs acquire an activated phenotype via various cytokines and promote tumor proliferation and growth, accelerate invasion and metastasis, induce angiogenesis, promote inflammation and immune destruction, regulate tumor metabolism, and induce chemoresistance; these factors contribute to the acquisition of major hallmarks of PDAC. Therefore, an improved understanding of the impact of CAFs on the major hallmarks of PDAC will highlight the diagnostic and therapeutic values of these targeted cells.

Keywords: pancreatic cancer, tumor microenvironment, hallmarks of cancer, cancer-associated fibroblast

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