Limits...
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.

Show MeSH

Related in: MedlinePlus

2-D projection of all variables, with the exception of TAF, at three time steps over the course of 6 months of invasion under the basic model.(A) The normal skin is largely intact, but a small epidermal tumor has displaced some of the surrounding healthy cells. (B) The tumor mass has been penetrated by the endothelial cells and, because of the associated degradation of the basement membrane, is invading vertically. The tumor is somewhat hypoxic, a core of necrotic debris has begun to form, and healthy cells continue to be displaced by the tumor. (C) A large tumor has invaded to the base of the domain and continues to expand radially. Hypoxia is most severe at the edge of invasion; this is reflected by the annular expansion of the necrotic core.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2667258&req=5

pcbi-1000362-g004: 2-D projection of all variables, with the exception of TAF, at three time steps over the course of 6 months of invasion under the basic model.(A) The normal skin is largely intact, but a small epidermal tumor has displaced some of the surrounding healthy cells. (B) The tumor mass has been penetrated by the endothelial cells and, because of the associated degradation of the basement membrane, is invading vertically. The tumor is somewhat hypoxic, a core of necrotic debris has begun to form, and healthy cells continue to be displaced by the tumor. (C) A large tumor has invaded to the base of the domain and continues to expand radially. Hypoxia is most severe at the edge of invasion; this is reflected by the annular expansion of the necrotic core.

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)

2-D projection of all variables, with the exception of TAF, at three time steps over the course of 6 months of invasion under the basic model.(A) The normal skin is largely intact, but a small epidermal tumor has displaced some of the surrounding healthy cells. (B) The tumor mass has been penetrated by the endothelial cells and, because of the associated degradation of the basement membrane, is invading vertically. The tumor is somewhat hypoxic, a core of necrotic debris has begun to form, and healthy cells continue to be displaced by the tumor. (C) A large tumor has invaded to the base of the domain and continues to expand radially. Hypoxia is most severe at the edge of invasion; this is reflected by the annular expansion of the necrotic core.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000362-g004: 2-D projection of all variables, with the exception of TAF, at three time steps over the course of 6 months of invasion under the basic model.(A) The normal skin is largely intact, but a small epidermal tumor has displaced some of the surrounding healthy cells. (B) The tumor mass has been penetrated by the endothelial cells and, because of the associated degradation of the basement membrane, is invading vertically. The tumor is somewhat hypoxic, a core of necrotic debris has begun to form, and healthy cells continue to be displaced by the tumor. (C) A large tumor has invaded to the base of the domain and continues to expand radially. Hypoxia is most severe at the edge of invasion; this is reflected by the annular expansion of the necrotic core.
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