Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

Figure 1

Lymphatic metastasis in PDAC: it is not a monodrama. Lymphatic metastasis is the concurrent effect of interaction among cancer cells, tumor microenvironment, and premetastatic site niche. The role of evolution of cancer cell and microenvironment in this abysmal biologic process is performed in a “double-reed” style. Under the influence of fertile microenvironment and accumulating gene alterations (KRAS, SMAD4, TP53+, Ink4a/Arf, etc.), a normal pancreatic epithelial cell underwent the long processes such as “acinar-to-ductal metaplasia” and “epithelia-mesenchymal transition” and finally sequentially forming a metastasis-initiating cell, which could initiate lymphatic metastasis under the guidance of specific chemokines (SDF-1, CCL19/CCL21, VEGF-C/D, etc.). Accordingly, potential therapeutic strategies targeted to the lymphatic metastasis of pancreatic cancer include: (1) targeting cancer cells (CSCs, MICs), (2) targeting molecules of signal pathways to the tumor, and (3) subverting the tumor microenvironments and niche.