Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.

By P. Hermann, Stephan L. Huber, T. Herrler, Alexandra Aicher, J. Ellwart, M. Guba, C. Bruns, C. Heeschen. Cell Stem Cell, 2007

2,917 citations recorded by the source corpus.

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.

Subfields: Oncology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/e06445e4ea5705a840ce9034b1294ace4a45b0e3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. R. Weinberg
2. J. Massagué
3. Zena Werb
4. Jane E. Visvader
5. Raghu Kalluri
6. M. Nieto
7. J. P. Thiery
8. J. Dick

In Psychiatry and Mental health

1. Zena Werb

Citations in the corpus

• Epithelial-mesenchymal transitions in development and disease. (2009, background): “In pancreatic carcinoma, there is evidence of the existence of two different stem cell-like populations: one that maintains the growth of the primary tumor and another that produces metastatic growth (Hermann et al., 2007).”
• Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs (2011, background): “The invasive front hosts presumptive cancer stem cells and dynamic interactions with mesenchymal, vascular and inflammatory components of the tumor strom”
• EMT and dissemination precede pancreatic tumor formation (2012, background): “In human pancreatic tumors, this activity may be contained within a CD24+CD44+ population of cells, among others (Hermann et al., 2007; Jimeno et al., 2009; Li et al., 2007).”
• The cancer stem cell: premises, promises and challenges (2011, background): “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 tumo”
• Cancer stem cells: current status and evolving complexities. (2012, background): “A similar story holds true for colorectal cancer in which the EpCAMhiCD44+ CSC subpopulation shared minor overlap with CD133 (Dalerba et al., 2007), and for pancreatic cancer, where overlap between the CD133+ and CD44+CD24+ populations varied considerably between specimens (Hermann et al., 2007).”
• CXCL12/CXCR4/CXCR7 Chemokine Axis and Cancer Progression (2010, background): “significantly reduces the metastatic phenotype of pancreatic tumors without affecting their tumorigenic potential, which indicates that a subpopulation of migrating CD133 CXCR4 cancer stem cells is essential for tumor metastasis [74].”
• Targeting TGF-β signal transduction for fibrosis and cancer therapy (2022, background): “This kind of deposition and infiltration accelerates the metastasis of pancreatic cancer cells and rationalizes early PDAC dissemination [163, 164].”
• Identification of Gastric Cancer Stem Cells Using the Cell Surface Marker CD44 (2009, methodology): “Based on previous published reports regarding CSCs in solid tumors [7–21], the following markers were studied: CD24, CD44, CD133, and CD166.”
• CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. (2014, background): “Human pancreatic CSCs expressing the putative stem cell marker CD133 and the chemokine receptor CXCR4 lost their metastatic activity when the CXCR4 population was depleted, suggesting that CSCs may hijack cytokine-regulated migration-signaling pathways to initiate metastasis (Hermann et al., 2007).”
• AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective (2010, positive): “A CSC origin has now been shown for a range of “liquid tumors” (192), including B- and T-acute lymphoblastic leukemia (B-ALL and T-ALL, respectively) and arguably with a variety of solid tumors (193).”
• CellMarker: a manually curated resource of cell markers in human and mouse (2018, methodology): “isolated pancreatic stem cells using the cell surface marker CD133 by standard flow cytometry (18).”