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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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Resection followed by metastatic recurrence.The primary tumor is held to a steady state and metastases are present at undetectable levels prior to resection. Following resection, aggressive metastatic recurrence occurs. The asymptotic behavior of the metastases is the same as the primary tumor (i.e. steady state), but the overall growth rate is faster, and the final cancer load is much greater.
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pcbi-1000362-g007: Resection followed by metastatic recurrence.The primary tumor is held to a steady state and metastases are present at undetectable levels prior to resection. Following resection, aggressive metastatic recurrence occurs. The asymptotic behavior of the metastases is the same as the primary tumor (i.e. steady state), but the overall growth rate is faster, and the final cancer load is much greater.

Mentions: The immune response is included in these simulations. If no treatment is performed the primary tumor invades normally while the metastases, if sufficiently close to the primary tumor, are generally destroyed or held to an extremely low density. We have found that if , then all metastases are typically suppressed. If the primary tumor is removed, any surviving metastases are often able to begin invading. The immune response eventually reacts to the metastases, and the same asymptotic behavior occurs (a steady-state is reached or the domain is invaded). However, the metastases often increase in total mass much more quickly than did the primary tumor. Such a course of treatment followed by metastatic recurrence is shown in Figures 7 and 8.


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

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

Resection followed by metastatic recurrence.The primary tumor is held to a steady state and metastases are present at undetectable levels prior to resection. Following resection, aggressive metastatic recurrence occurs. The asymptotic behavior of the metastases is the same as the primary tumor (i.e. steady state), but the overall growth rate is faster, and the final cancer load is much greater.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000362-g007: Resection followed by metastatic recurrence.The primary tumor is held to a steady state and metastases are present at undetectable levels prior to resection. Following resection, aggressive metastatic recurrence occurs. The asymptotic behavior of the metastases is the same as the primary tumor (i.e. steady state), but the overall growth rate is faster, and the final cancer load is much greater.
Mentions: The immune response is included in these simulations. If no treatment is performed the primary tumor invades normally while the metastases, if sufficiently close to the primary tumor, are generally destroyed or held to an extremely low density. We have found that if , then all metastases are typically suppressed. If the primary tumor is removed, any surviving metastases are often able to begin invading. The immune response eventually reacts to the metastases, and the same asymptotic behavior occurs (a steady-state is reached or the domain is invaded). However, the metastases often increase in total mass much more quickly than did the primary tumor. Such a course of treatment followed by metastatic recurrence is shown in Figures 7 and 8.

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