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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

A simple schematic of the modeled geometry.The epidermis is separated from the dermis by a sheet of basement membrane. At the base of the dermis is a vascular bed from which all endothelial cells migrate. Oxygen diffuses into the domain from the vascular bed and at the skin surface. The melanoma tumor originates in the epidermis. All other tissue is initially healthy cells.
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pcbi-1000362-g001: A simple schematic of the modeled geometry.The epidermis is separated from the dermis by a sheet of basement membrane. At the base of the dermis is a vascular bed from which all endothelial cells migrate. Oxygen diffuses into the domain from the vascular bed and at the skin surface. The melanoma tumor originates in the epidermis. All other tissue is initially healthy cells.

Mentions: Finally, the basement membrane separates the epidermis and dermis, serving as a barrier to migration for most cell types. The basement membrane is modeled using initial conditions in simulations - a thin strip of membrane is thought to exist at a depth of approximately 0.15 mm. A simple schematic of the modeled geometry is shown in Figure 1.


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

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

A simple schematic of the modeled geometry.The epidermis is separated from the dermis by a sheet of basement membrane. At the base of the dermis is a vascular bed from which all endothelial cells migrate. Oxygen diffuses into the domain from the vascular bed and at the skin surface. The melanoma tumor originates in the epidermis. All other tissue is initially healthy cells.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000362-g001: A simple schematic of the modeled geometry.The epidermis is separated from the dermis by a sheet of basement membrane. At the base of the dermis is a vascular bed from which all endothelial cells migrate. Oxygen diffuses into the domain from the vascular bed and at the skin surface. The melanoma tumor originates in the epidermis. All other tissue is initially healthy cells.
Mentions: Finally, the basement membrane separates the epidermis and dermis, serving as a barrier to migration for most cell types. The basement membrane is modeled using initial conditions in simulations - a thin strip of membrane is thought to exist at a depth of approximately 0.15 mm. A simple schematic of the modeled geometry is shown in Figure 1.

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