Like blood
vessels that supply oxygen and nutrients to normal tissue, tumor blood vessels
were originally thought to do likewise to fuel tumor growth. As scientists
developed strategies to kill tumors by cutting off their blood supply, they
soon discovered their valiant efforts were thwarted by the tumor's ability to
quickly recover.
The recovery is caused by a population of tumor-initiating
cancer cells dubbed the cancer stem cells (CSCs); a population that can
communicate with blood vessels via the Notch signaling pathway to drive tumor
vascularization.
It turns
out that this "Notch" communication can go both ways. In a Cancer Cell study, scientists discovered that
tumor-blood vessels can communicate with cancer cells via Notch signaling,
and direct their transformation into cancer stem cells. Specifically, the
authors found that when colorectal cancer cells are exposed to tumor
endothelial cell directly or indirectly via conditioned medium, these cells
acquire features that resemble CSCs.
Some of these features include their
expression of the stem cell marker CD133, their ability to initiate colorectal
cancer when transplanted elsewhere, and their marked resistance to
chemotherapy.
The authors
further found that the Notch signaling is driven by the release of soluble
Jagged-1 from the surface of endothelial cells, a process driven by a membrane
enzyme ADAM17. Jagged-1 binds to Notch-1 and triggers downstream activation of
the transcription factors Hes1 and NICD in cancer cells to drive their
transformation into CSCs.
Supporting
this preclinical data, the authors found that colorectal CSCs are closely
associated tumor blood vessels in clinical surgical specimens of colorectal
cancer. Using a Notch signaling reporter system to track Hes1 and NICD in
surgical specimens, the authors were able to confirm that Notch signaling is
indeed active in colorectal cancer cells/stem cells surrounding tumor blood
vessels.
This study first
evidence suggesting that tumor-blood vessels are not merely conduits of
nutrients and oxygen, but are also a communication hub that orchestrates the
birth of cancer stem cells- the drivers of tumor initiation.
Reference:
Lu et al., Endothelial Cells Promote the Colorectal Cancer
Stem Cell Phenotype through a Soluble Form of Jagged-1, Cancer Cell (2013),