Role of interstitial flow in tumor migration through 3D ECM

Cancer invasion in tissue is simultaneously regulated by chemical and mechanical cues.Evidences suggest that interstitial flow plays a critical role in tumor metastasis.On one hand,the distribution of chemokines around cell is influenced by flow.On the other hand,interstitial flow may reconfigure the alignment of fiber matrix,which greatly changes the contact force between cell and extracellular matrix.In this study,we have upgraded a model by which we can quantitatively investigate the influence of flow on tumor cell migration.A hydrodynamic analysis of shear stress on a slender body is introduced to simulate the fiber realignment.Factors such as subtle flow and cell-matrix interaction which dominate tumor migration are integrated in this novel model.Simulation results show interstitial flow facilitates tumor cell migration in the flow direction.Moreover,the flow-related chemical and mechanical cues have a synergistic effect on the migration.This model provides better understanding on cancer metastasis and helps design vitro experiment precisely.

Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.