Limits...
Ecology meets cancer biology: the cancer swamp promotes the lethal cancer phenotype.

Amend SR, Pienta KJ - Oncotarget (2015)

Bottom Line: As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole.Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient.These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.

ABSTRACT
As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole. Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient. These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death). In particular, as cancer cells generate their own niche within the tumor ecosystem, ecological engineering and autoeutrophication displace normal cell function and result in the creation of a hypoxic, acidic, and nutrient-poor environment. This "cancer swamp" has genetic and epigenetic effects at the local ecosystem level to promote metastasis and at the systemic host level to induce cytokine-mediated lethal syndromes, a major cause of death of cancer patients.

No MeSH data available.


Related in: MedlinePlus

Autoeutrophication of the hypoxic, nutrient-poor, and acidic “cancer swamp”(Left) Excess nitrogen and phosphorus deposits stimulate the growth of photosynthetic algae, resulting in a characteristic algal bloom. As the algae die off, organic material accumulates and decomposition levels increase, leading to severe hypoxia. These harsh conditions select for efficient anaerobic decomposers. The build-up of the waste product of anaerobic fermentation, carbon dioxide, results in an acidic environment. Ultimately, the severe conditions lead to the local extinction of native species and eventual irreversible ecosystem collapse. (Right) Even in the absence of external stimuli, cancer cells have a high proliferation rate, rapidly expanding to a tumor mass analogous to an algal bloom. As the tumor grows, it quickly outstrips its vascular supply, resulting in a hypoxic microenvironment. To survive, the cancer cells alter their metabolism to utilize relatively inefficient anaerobic glycolysis, exhausting available nutrient sources. The accumulation of lactic acid, the waste product of anaerobic glycolysis, results in an acidic microenvironment. Ultimately, the harsh “cancer swamp” selects for highly lethal cancer superclones. Simultaneously, the toxic conditions lead to increased rates of necrosis, extinction of native host cell types, and eventual organ failure.
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Figure 1: Autoeutrophication of the hypoxic, nutrient-poor, and acidic “cancer swamp”(Left) Excess nitrogen and phosphorus deposits stimulate the growth of photosynthetic algae, resulting in a characteristic algal bloom. As the algae die off, organic material accumulates and decomposition levels increase, leading to severe hypoxia. These harsh conditions select for efficient anaerobic decomposers. The build-up of the waste product of anaerobic fermentation, carbon dioxide, results in an acidic environment. Ultimately, the severe conditions lead to the local extinction of native species and eventual irreversible ecosystem collapse. (Right) Even in the absence of external stimuli, cancer cells have a high proliferation rate, rapidly expanding to a tumor mass analogous to an algal bloom. As the tumor grows, it quickly outstrips its vascular supply, resulting in a hypoxic microenvironment. To survive, the cancer cells alter their metabolism to utilize relatively inefficient anaerobic glycolysis, exhausting available nutrient sources. The accumulation of lactic acid, the waste product of anaerobic glycolysis, results in an acidic microenvironment. Ultimately, the harsh “cancer swamp” selects for highly lethal cancer superclones. Simultaneously, the toxic conditions lead to increased rates of necrosis, extinction of native host cell types, and eventual organ failure.

Mentions: Eutrophication is the enrichment of an ecosystem with chemical or organic nutrients. Eutrophication is considered a healthy process when it occurs slowly on a geological time scale as part of the natural aging of a lake to a productive meadow [24]. When accelerated, however, eutrophication dismantles normal nutrient cycling and litter feedbacks, resulting in altered species stoichiometry and, if left unchecked, ecosystem failure [25]. Human acceleration of eutrophication (cultural eutrophication) of watersheds is one of the most apparent examples of forced acyclic nutrient cycling [10, 26]. Pollution in the form of fertilizers and sewage leads to local nutrient enrichment, specifically of phosphorus and nitrogen, two of the limiting growth factors necessary for photosynthesis [27]. The rapid accumulation of excess nutrients accelerates the creation of a swamp by inducing acyclic resource recycling that leads to the growth and expansion of photosynthetic organisms such as short-lived cyanobacteria that compose characteristic algal blooms. As the organic material of these algae accumulates, decomposition levels increase, consuming high levels of oxygen and leading to severe hypoxic conditions. The oxygen-poor environment is unable to support native consumer species such as fish or mollusks and is colonized by detritus-feeders (Figure 1). Nutrient cycling becomes weighted towards the activities of producers and lacks the negative feedback from consumer species. In addition, algae blooms may also directly poison consumer species, further exacerbating acyclic resource cycling [28, 29]. Such an ecosystem is unstable and susceptible to irreversible collapse.


Ecology meets cancer biology: the cancer swamp promotes the lethal cancer phenotype.

Amend SR, Pienta KJ - Oncotarget (2015)

Autoeutrophication of the hypoxic, nutrient-poor, and acidic “cancer swamp”(Left) Excess nitrogen and phosphorus deposits stimulate the growth of photosynthetic algae, resulting in a characteristic algal bloom. As the algae die off, organic material accumulates and decomposition levels increase, leading to severe hypoxia. These harsh conditions select for efficient anaerobic decomposers. The build-up of the waste product of anaerobic fermentation, carbon dioxide, results in an acidic environment. Ultimately, the severe conditions lead to the local extinction of native species and eventual irreversible ecosystem collapse. (Right) Even in the absence of external stimuli, cancer cells have a high proliferation rate, rapidly expanding to a tumor mass analogous to an algal bloom. As the tumor grows, it quickly outstrips its vascular supply, resulting in a hypoxic microenvironment. To survive, the cancer cells alter their metabolism to utilize relatively inefficient anaerobic glycolysis, exhausting available nutrient sources. The accumulation of lactic acid, the waste product of anaerobic glycolysis, results in an acidic microenvironment. Ultimately, the harsh “cancer swamp” selects for highly lethal cancer superclones. Simultaneously, the toxic conditions lead to increased rates of necrosis, extinction of native host cell types, and eventual organ failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496388&req=5

Figure 1: Autoeutrophication of the hypoxic, nutrient-poor, and acidic “cancer swamp”(Left) Excess nitrogen and phosphorus deposits stimulate the growth of photosynthetic algae, resulting in a characteristic algal bloom. As the algae die off, organic material accumulates and decomposition levels increase, leading to severe hypoxia. These harsh conditions select for efficient anaerobic decomposers. The build-up of the waste product of anaerobic fermentation, carbon dioxide, results in an acidic environment. Ultimately, the severe conditions lead to the local extinction of native species and eventual irreversible ecosystem collapse. (Right) Even in the absence of external stimuli, cancer cells have a high proliferation rate, rapidly expanding to a tumor mass analogous to an algal bloom. As the tumor grows, it quickly outstrips its vascular supply, resulting in a hypoxic microenvironment. To survive, the cancer cells alter their metabolism to utilize relatively inefficient anaerobic glycolysis, exhausting available nutrient sources. The accumulation of lactic acid, the waste product of anaerobic glycolysis, results in an acidic microenvironment. Ultimately, the harsh “cancer swamp” selects for highly lethal cancer superclones. Simultaneously, the toxic conditions lead to increased rates of necrosis, extinction of native host cell types, and eventual organ failure.
Mentions: Eutrophication is the enrichment of an ecosystem with chemical or organic nutrients. Eutrophication is considered a healthy process when it occurs slowly on a geological time scale as part of the natural aging of a lake to a productive meadow [24]. When accelerated, however, eutrophication dismantles normal nutrient cycling and litter feedbacks, resulting in altered species stoichiometry and, if left unchecked, ecosystem failure [25]. Human acceleration of eutrophication (cultural eutrophication) of watersheds is one of the most apparent examples of forced acyclic nutrient cycling [10, 26]. Pollution in the form of fertilizers and sewage leads to local nutrient enrichment, specifically of phosphorus and nitrogen, two of the limiting growth factors necessary for photosynthesis [27]. The rapid accumulation of excess nutrients accelerates the creation of a swamp by inducing acyclic resource recycling that leads to the growth and expansion of photosynthetic organisms such as short-lived cyanobacteria that compose characteristic algal blooms. As the organic material of these algae accumulates, decomposition levels increase, consuming high levels of oxygen and leading to severe hypoxic conditions. The oxygen-poor environment is unable to support native consumer species such as fish or mollusks and is colonized by detritus-feeders (Figure 1). Nutrient cycling becomes weighted towards the activities of producers and lacks the negative feedback from consumer species. In addition, algae blooms may also directly poison consumer species, further exacerbating acyclic resource cycling [28, 29]. Such an ecosystem is unstable and susceptible to irreversible collapse.

Bottom Line: As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole.Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient.These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.

ABSTRACT
As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole. Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient. These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death). In particular, as cancer cells generate their own niche within the tumor ecosystem, ecological engineering and autoeutrophication displace normal cell function and result in the creation of a hypoxic, acidic, and nutrient-poor environment. This "cancer swamp" has genetic and epigenetic effects at the local ecosystem level to promote metastasis and at the systemic host level to induce cytokine-mediated lethal syndromes, a major cause of death of cancer patients.

No MeSH data available.


Related in: MedlinePlus