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Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles.

Chen KW, Pienta KJ - Theor Biol Med Model (2011)

Bottom Line: These modified equations allow a more flexible way to model the space competition between the two cell species.The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations.These equations are currently being applied to clinical data sets for verification and further refinement of the models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, The University of Michigan, 7308 CCC, 1500 E, Medical Center Drive, Ann Arbor, MI 48109, USA. kpienta@umich.edu

ABSTRACT

Background: The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact).

Results: Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells.

Conclusions: The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.

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Population biology of invasive species and metastasis. The generalized steps necessary for a species to invade a new ecologic niche are directly analogous to the steps of cancer metastasis (modified from Sakai and colleagues [4]). The transport, establishment, and spread of invasive species can be compared to the intravasation of cancer cells into the blood stream where they are transported to a target organ where they extravasate. The cancer cells then enter a dormant period (lag period for invasive species) before growing, and displacing the host cells (native species). This results in damage to the local organ and eventually the host patient (human impact).
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Figure 1: Population biology of invasive species and metastasis. The generalized steps necessary for a species to invade a new ecologic niche are directly analogous to the steps of cancer metastasis (modified from Sakai and colleagues [4]). The transport, establishment, and spread of invasive species can be compared to the intravasation of cancer cells into the blood stream where they are transported to a target organ where they extravasate. The cancer cells then enter a dormant period (lag period for invasive species) before growing, and displacing the host cells (native species). This results in damage to the local organ and eventually the host patient (human impact).

Mentions: The life cycle of invasive species is directly analogous to the study of cancer metastasis [Figure 1] [4-10]. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate at a target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact) [11-13]. Studies of the population biology of invasive species have allowed a more precise focus on specific characteristics involved in invasiveness [14-16]. Tilman has described mathematical equations for the competition between species in a structured habitat [16]. These equations can be adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. Within the bone marrow microenvironment, hematopoietic stem cells (HSC) homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish footholds in the bone marrow. Recent evidence suggests that tumor cells target and parasitize the HSC niche during metastasis just as invasive species do in the world [17]. We adapted the Tilman model of invasion dynamics to model cancer cell metastasis to the bone marrow microenvironment.


Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles.

Chen KW, Pienta KJ - Theor Biol Med Model (2011)

Population biology of invasive species and metastasis. The generalized steps necessary for a species to invade a new ecologic niche are directly analogous to the steps of cancer metastasis (modified from Sakai and colleagues [4]). The transport, establishment, and spread of invasive species can be compared to the intravasation of cancer cells into the blood stream where they are transported to a target organ where they extravasate. The cancer cells then enter a dormant period (lag period for invasive species) before growing, and displacing the host cells (native species). This results in damage to the local organ and eventually the host patient (human impact).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198921&req=5

Figure 1: Population biology of invasive species and metastasis. The generalized steps necessary for a species to invade a new ecologic niche are directly analogous to the steps of cancer metastasis (modified from Sakai and colleagues [4]). The transport, establishment, and spread of invasive species can be compared to the intravasation of cancer cells into the blood stream where they are transported to a target organ where they extravasate. The cancer cells then enter a dormant period (lag period for invasive species) before growing, and displacing the host cells (native species). This results in damage to the local organ and eventually the host patient (human impact).
Mentions: The life cycle of invasive species is directly analogous to the study of cancer metastasis [Figure 1] [4-10]. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate at a target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact) [11-13]. Studies of the population biology of invasive species have allowed a more precise focus on specific characteristics involved in invasiveness [14-16]. Tilman has described mathematical equations for the competition between species in a structured habitat [16]. These equations can be adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. Within the bone marrow microenvironment, hematopoietic stem cells (HSC) homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish footholds in the bone marrow. Recent evidence suggests that tumor cells target and parasitize the HSC niche during metastasis just as invasive species do in the world [17]. We adapted the Tilman model of invasion dynamics to model cancer cell metastasis to the bone marrow microenvironment.

Bottom Line: These modified equations allow a more flexible way to model the space competition between the two cell species.The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations.These equations are currently being applied to clinical data sets for verification and further refinement of the models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, The University of Michigan, 7308 CCC, 1500 E, Medical Center Drive, Ann Arbor, MI 48109, USA. kpienta@umich.edu

ABSTRACT

Background: The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact).

Results: Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells.

Conclusions: The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.

Show MeSH
Related in: MedlinePlus