An interesting new aspect to the pathogenesis of metastasis was discovered by researchers from the Memorial Sloan-Kettering Cancer Center and the Weill Medical College. From the press release by Howard Hughes Medical Institute:
Howard Hughes Medical Institute researchers and their colleagues have discovered that non-malignant bone marrow cells establish “cellular bookmarks” in target organs that guide the spread of cancer cells to their predetermined destination.
The researchers said their findings could have a major impact on how oncologists assess the likeliness of metastasis to specific organs. Their discovery may also help identify subsets of high risk cancer patients who are prone to distant metastases. Those patients would likely benefit from a more aggressive adjuvant therapy to prevent cancer relapse.
The researchers, led by David Lyden and Rafii, published their findings in the December 8, 2005, issue of the journal Nature.
Rafii and Lyden’s group had established that a specific subset of bone marrow derived cells (BMDCs ) – which are comprised of hematopoietic progenitor cells capable of dividing and forming colonies – are recruited by tumors to aid in the growth of new blood vessels. The generation of new blood vessels occurs through a process called angiogenesis. In previous studies, the researchers had shown that co-recruitment of hematopoietic BMDCs expressing the angiogenic factor receptor, VEGFR1, along with the vascular cells accelerated the assembly of newly formed blood vessels and tumor growth.
“In the current paper, we set forth another novel concept by demonstrating that a non-malignant cluster of VEGFR1-positive hematopoietic BMDCs were recruited to a pre-metastatic niche, thereby establishing a permissive docking site prior to the arrival of the circulating tumor cells,” said Rafii.
In experiments with mice that had been implanted with highly metastatic lung cancers or melanoma cells, the scientists discovered that BMDCs did, indeed, arrive at the pre-metastatic sites before the arrival of cancer cells. The researchers also found that such clusters appeared prior to the development of metastases in mice genetically predisposed to developing tumors – a system that closely mimics how cancers develop.
The researchers showed that interference with the mobilization of VEGFR1-positive cells from the bone marrow and incorporation into the pre-metastatic niche resulted in a significant decrease in subsequent tumor metastasis.