Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer

Abstract

Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Stem cells have been implicated in pancreatic tumor growth, but the specific role of these cancer stem cells in tumor biology, including metastasis, is still uncertain. We found that human pancreatic cancer tissue contains cancer stem cells defined by CD133 expression that are exclusively tumorigenic and highly resistant to standard chemotherapy. In the invasive front of pancreatic tumors, a distinct subpopulation of CD133(+) CXCR4(+) cancer stem cells was identified that determines the metastatic phenotype of the individual tumor. Depletion of the cancer stem cell pool for these migrating cancer stem cells virtually abrogated the metastatic phenotype of pancreatic tumors without affecting their tumorigenic potential. In conclusion, we demonstrate that a subpopulation of migrating CD133(+) CXCR4(+) cancer stem cells is essential for tumor metastasis. Strategies aimed at modulating the SDF-1/CXCR4 axis may have important clinical applications to inhibit metastasis of cancer stem cells.

DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell

“…In addition, pancreatic cancer cells might acquire stemness or express ‘stem cell‐like’ properties under hypoxia, consequently leading to an aggressive phenotype 42. A previous study confirmed that hypoxia induced an increased number of invading CD133 + pancreatic cancer cells 42, a marker typically used to identify and isolate human pancreatic cancer stem cells 43. Thus, we wondered whether DKK3 has an effect on EMT and stem cell properties in pancreatic cancer.…”

Chemokines in cancer related inflammation

“…CXCR4+ CSC have been isolated from glioblastoma [91] and pancreas [94]. In this latter case, a distinct subpopulation of CD133+/CXCR4+ CSC was identified at the invasive front of the tumor and determined the metastatic phenotype of individual tumors [94].…”

Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

“…Pancreatic cancer stem cells, profiled as CD133 þ CXCR4 þ , exhibited significantly stronger migratory activity in vitro (Hermann et al, 2007). Furthermore, CD44 þ CD24 À/low cells, a cancer-initiating subset of breast cancer, are readily detectable in pleural effusions in breast cancer patients (Al-Hajj et al, 2003).…”