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Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma.

Eikenberry S, Thalhauser C, Kuang Y - PLoS Comput. Biol. (2009)

Bottom Line: Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic.Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue.This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona, USA. seikenbe@asu.edu

ABSTRACT
Malignant melanoma is a cancer of the skin arising in the melanocytes. We present a mathematical model of melanoma invasion into healthy tissue with an immune response. We use this model as a framework with which to investigate primary tumor invasion and treatment by surgical excision. We observe that the presence of immune cells can destroy tumors, hold them to minimal expansion, or, through the production of angiogenic factors, induce tumorigenic expansion. We also find that the tumor-immune system dynamic is critically important in determining the likelihood and extent of tumor regrowth following resection. We find that small metastatic lesions distal to the primary tumor mass can be held to a minimal size via the immune interaction with the larger primary tumor. Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic. Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue. This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state. These results are in line with clinical case studies involving resection of a primary melanoma followed by recurrence in local metastases.

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Related in: MedlinePlus

1-D projection of variables densities at the inner radius of the domain.Time steps are evenly spaced over roughly 4.5 months of invasion under the basic model. (A) The seed of a tumor has been planted at the base of the epidermis. (B) The tumor has expanded vertically into the upper epidermis, and has increased in density due to cancer cells out-competing the healthy cells. (C) Here, the basement membrane has been eliminated, and the tumor invades vertically into the existing tumor-associated vasculature. (D) A significant necrotic core has formed roughly in the center of the vertical domain, very few healthy cells remain, and cancer cells continue to grow into the tumor vasculature.
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pcbi-1000362-g005: 1-D projection of variables densities at the inner radius of the domain.Time steps are evenly spaced over roughly 4.5 months of invasion under the basic model. (A) The seed of a tumor has been planted at the base of the epidermis. (B) The tumor has expanded vertically into the upper epidermis, and has increased in density due to cancer cells out-competing the healthy cells. (C) Here, the basement membrane has been eliminated, and the tumor invades vertically into the existing tumor-associated vasculature. (D) A significant necrotic core has formed roughly in the center of the vertical domain, very few healthy cells remain, and cancer cells continue to grow into the tumor vasculature.

Mentions: To thoroughly demonstrate the model results, a 3-D isosurface of the evolution of three key variables, cancer cells, basement membrane, and endothelial cells, over several months of invasion is shown in Figure 3. A 2-D projection of the same simulation is shown in Figure 4. Finally, a 1-D projection of variable densities at the inner radius of the domain is shown in Figure 5.


Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma.

Eikenberry S, Thalhauser C, Kuang Y - PLoS Comput. Biol. (2009)

1-D projection of variables densities at the inner radius of the domain.Time steps are evenly spaced over roughly 4.5 months of invasion under the basic model. (A) The seed of a tumor has been planted at the base of the epidermis. (B) The tumor has expanded vertically into the upper epidermis, and has increased in density due to cancer cells out-competing the healthy cells. (C) Here, the basement membrane has been eliminated, and the tumor invades vertically into the existing tumor-associated vasculature. (D) A significant necrotic core has formed roughly in the center of the vertical domain, very few healthy cells remain, and cancer cells continue to grow into the tumor vasculature.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2667258&req=5

pcbi-1000362-g005: 1-D projection of variables densities at the inner radius of the domain.Time steps are evenly spaced over roughly 4.5 months of invasion under the basic model. (A) The seed of a tumor has been planted at the base of the epidermis. (B) The tumor has expanded vertically into the upper epidermis, and has increased in density due to cancer cells out-competing the healthy cells. (C) Here, the basement membrane has been eliminated, and the tumor invades vertically into the existing tumor-associated vasculature. (D) A significant necrotic core has formed roughly in the center of the vertical domain, very few healthy cells remain, and cancer cells continue to grow into the tumor vasculature.
Mentions: To thoroughly demonstrate the model results, a 3-D isosurface of the evolution of three key variables, cancer cells, basement membrane, and endothelial cells, over several months of invasion is shown in Figure 3. A 2-D projection of the same simulation is shown in Figure 4. Finally, a 1-D projection of variable densities at the inner radius of the domain is shown in Figure 5.

Bottom Line: Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic.Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue.This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona, USA. seikenbe@asu.edu

ABSTRACT
Malignant melanoma is a cancer of the skin arising in the melanocytes. We present a mathematical model of melanoma invasion into healthy tissue with an immune response. We use this model as a framework with which to investigate primary tumor invasion and treatment by surgical excision. We observe that the presence of immune cells can destroy tumors, hold them to minimal expansion, or, through the production of angiogenic factors, induce tumorigenic expansion. We also find that the tumor-immune system dynamic is critically important in determining the likelihood and extent of tumor regrowth following resection. We find that small metastatic lesions distal to the primary tumor mass can be held to a minimal size via the immune interaction with the larger primary tumor. Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic. Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue. This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state. These results are in line with clinical case studies involving resection of a primary melanoma followed by recurrence in local metastases.

Show MeSH
Related in: MedlinePlus