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abstract
"Cancer cells that disseminate to metastatic sites may progress to frank metastasis or persist as dormant micrometastasis. Significant progress has been made in defining the genetic and phenotypic cancer-cell-autonomous determinants of metastasis and in the understanding of the cross-talk between metastasizing tumor cells and the metastatic microenvironment.
However several questions remain open, in particular the identity of microenvironmental factors that keep micrometastatic cells in a state of dormancy and those that promote survival, proliferation and progression of such cells. Significantly more information is available on the latter factors than on microenvironmental cells and molecules that restrain micrometastasis. This mini-review summarizes findings suggesting that:
•The
interactions between the metastatic microenvironment and cancer cells
metastasizing to this microenvironment are unique to each metastatic
microenvironment.
•cells or molecules in the metastatic microenvironment could act as "double agents" exerting pro- or anti-malignant functions.
•In
the early phases of tumor progression, the interactions between cancer
cells and the metastatic microenvironment are inhibitory whereas in
later stages such interactions promote progression towards metastasis.
In view of the above, it is not unlikely that metastases residing in different microenvironments may require “individualized” treatment modalities."
In regards to frank or dormant micrometastasis, even those malignant characters that manage to slither their way into the blood or lymph system usually fail to do anything further. Most tumor cells lack the streamlined form of the blood and immune cells that are designed for cross-body trafficking, shear forces in the smaller vessels may rip the intruders apart.
ReplyDeleteThe microenvironment contributes critically to drug response. By examining drug-induced cell death events in native-state 3D (three dimensional) microclusters, the functional profiling platform (phenotype analysis) has the unique capacity to capture stromal, cytokines (chemokines), macrophages, lymphocytes, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction.
The microclusters recapitulate the human tumor environment, while the "3D" advancement recreates the extracellular matrix (metalloproteinases). The platform studies cancer response to drugs within this microenvironment, enabling it to provide clinically relevant predictions to cancer patients. It is this capacity to study human tumor microenvironments that distinguishes it from other platforms in the field.