Hematogeneous Metastasis
Metastasis: Hematogeneous Several interdependent mechanisms influence the metastatic cascade, and despite the impressive rate of publication in this area (> 10,000 hits on Medline from 2000 to 2006), we still know little about the key steps in the process. An outstanding question in the field of metastasis is whether cancer cells need to actively adhere to and migrate out of blood vessels at the secondary site in order to colonize. On the one hand, we know that cancer cells express endothelial adhesion receptors, similar to leukocytes, that allow them to roll on and adhere to endothelium. But other studies have found clumps of cancer cells surviving and growing within the lumen of blood vessels at the secondary site.
These disparate observations suggest that some manifestations of metastasis are actively enabled by cancer cells, but others may be dictated by chance. The above example pertains to the later stages of metastasis, but we propose that similar considerations apply during the initial, intravasation step as well.
Active and passive mechanisms in the initial steps of metastasis. Left: In support of active metastasis are reports that cancer cells accumulate mutations, upregulate migration machinery, align and migrate up nutrient or chemokine gradients. It is also likely that fibroblasts, macrophages or other stromal cells cooperate with cancer cells to actively facilitate the initial stage of metastasis. Right: On the other hand, there is evidence that many dead cells are shed into the vasculature, which implies a passive mechanism. It is possible that uncontrolled focal growth crushes or impinges upon fragile tumour blood vessels, leading to passive shedding.