Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jul 30;17(1):108.
doi: 10.1186/s12943-018-0858-1.

Tumor microenvironment participates in metastasis of pancreatic cancer

Bo Ren  1 , Ming Cui  1 , Gang Yang  1 , Huanyu Wang  1 , Mengyu Feng  1 , Lei You  2 , Yupei Zhao  3
Affiliations
Review

Tumor microenvironment participates in metastasis of pancreatic cancer

Bo Ren et al. Mol Cancer. .

Abstract

Pancreatic cancer is a deadly disease with high mortality due to difficulties in its early diagnosis and metastasis. The tumor microenvironment induced by interactions between pancreatic epithelial/cancer cells and stromal cells is critical for pancreatic cancer progression and has been implicated in the failure of chemotherapy, radiation therapy and immunotherapy. Microenvironment formation requires interactions between pancreatic cancer cells and stromal cells. Components of the pancreatic cancer microenvironment that contribute to desmoplasia and immunosuppression are associated with poor patient prognosis. These components can facilitate desmoplasia and immunosuppression in primary and metastatic sites or can promote metastasis by stimulating angiogenesis/lymphangiogenesis, epithelial-mesenchymal transition, invasion/migration, and pre-metastatic niche formation. Some molecules participate in both microenvironment formation and metastasis. In this review, we focus on the mechanisms of pancreatic cancer microenvironment formation and discuss how the pancreatic cancer microenvironment participates in metastasis, representing a potential target for combination therapy to enhance overall survival.

Keywords: Desmoplasia; Immunosuppression; Metastasis; Pancreatic cancer; Tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Development of the pancreatic cancer microenvironment. Pancreatic cancer cells secrete cytokines and chemokines to recruit or activate stromal cells for desmoplasia and immune evasion, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and pancreatic stellate cells (PSCs). Among them, PSCs are the main source of ECM deposition, and the TAM-PSC axis can facilitate desmoplasia. These cells within the pancreatic cancer microenvironment can help pancreatic cancer cells inhibit CD8+ T cells to overcome the immune surveillance by expressing or producing various factors, such as IL-10, TGFβ, PD-L1, and IDO
Fig. 2
Fig. 2
The pancreatic cancer microenvironment participates in metastasis. The pancreatic cancer microenvironment influences every step of metastasis via multiple signaling pathways. (1) The pancreatic cancer microenvironment can stimulate angiogenesis by cytokines to favor cancer cell survival and proliferation. (2) Molecules from the pancreatic cancer microenvironment can induce lymphangiogenesis to establish a pathway for lymphatic metastasis. (3) The pancreatic cancer microenvironment can facilitate the epithelial-mesenchymal transition to cause cancer cells to enter lymphatic vessel. (4) The pancreatic cancer microenvironment can play important roles in invasion and migration to facilitate metastasis. (5) Factors and exosomes derived from the pancreatic cancer microenvironment can induce pre-metastatic niche formation in liver and lung. These molecules or exosomes can activate hepatic stellate cells (HSCs) in liver for desmoplasia
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. doi: 10.3322/caac.21442. - DOI - PubMed
    1. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801–1806. doi: 10.1126/science.1164368. - DOI - PMC - PubMed
    1. Chronopoulos A, Robinson B, Sarper M, Cortes E, Auernheimer V, Lachowski D, Attwood S, Garcia R, Ghassemi S, Fabry B, Del Rio HA. ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion. Nat Commun. 2016;7:12630. doi: 10.1038/ncomms12630. - DOI - PMC - PubMed
    1. Neesse A, Algül H, Tuveson DA, Gress TM. Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut. 2015;64:1476–1484. doi: 10.1136/gutjnl-2015-309304. - DOI - PubMed
    1. Ayala G, Tuxhorn JA, Wheeler TM, Frolov A, Scardino PT, Ohori M, Wheeler M, Spitler J, Rowley DR. Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clin Cancer Res. 2003;9:4792–4801. - PubMed

Publication types

Substances