Ultimately, to metastasize,
a cancer cell must move from its native ecosystem of the primary tumor.
Dispersal, both in ecology and in cancer biology, is a high risk endeavor.
The risks associated with movement have been described in the field of movement
ecology and include decreased short term fitness of the emigrant.
Or in this case cancer cell, loss of the ability replicate
because once the cancer cell is moving it can no longer replicate while it's moving.
Change in metabolism.
Energy spent to transition to a migratory phenotype.
It takes a lot of energy for a cell to move, unfamiliar and
hostile environment, which has increased predation and
ecology but also increased immune surveillance in cancer metastasis.
And future risk of a hostile secondary site or no secondary environment at all.
So this high level of risk means that individuals, or cancer cells,
do not leave their native ecosystems unless the risks of remaining in
the ecosystem are higher than the risks associated with dispersal.
One of the major reasons why organisms vacate their native ecosystem is
because conditions deteriorate rapidly due to outside forces
influencing the ecosystem and eventually leading to ecosystem collapse.
Here we show an example of a eutrophic watershed.
That was instigated by pollution from fertilizer and untreated sewage.
Pollution leads to invasive algae growth, increase algae proliferation and
decay causes hypoxic, acidic and nutrient poor conditions.
So non native organisms that survive in the harsh conditions are selected for.
Native species go extinct or migrate to a secondary site.
In this decoupled ecosystem, organisms must either disperse from the harsh
conditions to find a more favorable secondary site or they go extinct.
A similar mechanism is at play in the primary tumor
ecosystem in a cancer patient.
Unlike rapid ecological eutrophication, in a tumor the rapidly
proliferating cancer cells form a tumor that both instigates and
maintains the harmful so-called autoeutrophic environment.
Eventually as the tumor outstrips the vasculature, normal ecosystem homeostasis
is dismantled resulting in a hypoxic, acidic and nutrient poor habitat.
What we have termed the cancer swamp.
Like the selection for anaerobic decomposers of the ecological setting,
these conditions select for cancer cells that thrive in the harsh conditions
of the tumor and lead to extinction of native species, or normal cells.
Eventually as overcrowding increases and oxygen, pH, and nutrient levels decrease,
cancer cells are induced to leave the primary tumor as a metastatic cell.
Research in our group is working to understand each of these steps,
from the formation of the cancer swamp to the ecosystem influences that induce cells
to eventually disperse from the primary site, with the goal of understanding this
first critical step of the metastatic progression.
In addition to the example I outlined here, we and
others are applying ecological paradise to other components of cancer biology in
order to gain new insight into the metastatic problem.
For example, active research is using ecological models to study engineering of
the tumor microenvironment, movement ecology of metastatic cells, so
why they move and how they move.
Ability of circulating tumor cells to survive in transit, which we talked about.
Causes of the cytokine mediated syndromes, a major cause of death in cancer patients.
And designs of novel ecotherapy drugs to dismantle cancer ecosystems.
So in this lecture, we've discussed metastasis, we've defined metastasis,
we've defined the TNM staging system, and metastasis' role in that,
the metastatic cascade, and also novel paradigms that research groups
are working on to try to find underlying mechanisms of metastasis.
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