Tumor-Immune Interaction, Surgical Treatment, and Cancer Recurrence in a Mathematical Model of Melanoma

被引:57
作者
Eikenberry, Steffen [1 ]
Thalhauser, Craig [2 ]
Kuang, Yang [1 ]
机构
[1] Arizona State Univ, Dept Math & Stat, Tempe, AZ 85287 USA
[2] Univ Calif Irvine, Dept Math, Irvine, CA 92717 USA
关键词
ENDOTHELIAL GROWTH-FACTOR; CELL-GROWTH; ANGIOGENESIS; METASTASIS; OXYGEN; XENOGRAFTS; DIFFUSION; KINETICS; VASCULOGENESIS; PROLIFERATION;
D O I
10.1371/journal.pcbi.1000362
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:18
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共 50 条
[1]   Continuous and discrete mathematical models of tumor-induced angiogenesis [J].
Anderson, ARA ;
Chaplain, MAJ .
BULLETIN OF MATHEMATICAL BIOLOGY, 1998, 60 (05) :857-899
[2]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[3]   MIGRATION AND PROLIFERATION OF ENDOTHELIAL CELLS IN PREFORMED AND NEWLY FORMED BLOOD-VESSELS DURING TUMOR ANGIOGENESIS [J].
AUSPRUNK, DH ;
FOLKMAN, J .
MICROVASCULAR RESEARCH, 1977, 14 (01) :53-65
[4]   A mathematical model for the regulation of tumor dormancy based on enzyme kinetics [J].
Boushaba, Khalid ;
Levine, Howard A. ;
Nilsen-Hamilton, Marit .
BULLETIN OF MATHEMATICAL BIOLOGY, 2006, 68 (07) :1495-1526
[5]  
Brown JM, 1998, CANCER RES, V58, P1408
[6]   Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing [J].
Cárdenas-Navia, LI ;
Yu, DH ;
Braun, RD ;
Brizel, DM ;
Secomb, TW ;
Dewhirst, MW .
CANCER RESEARCH, 2004, 64 (17) :6010-6017
[7]   Mathematical modelling of angiogenesis [J].
Chaplain, MAJ .
JOURNAL OF NEURO-ONCOLOGY, 2000, 50 (1-2) :37-51
[8]   Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation [J].
Chen, Ruth R. ;
Silva, Eduardo A. ;
Yuen, William W. ;
Mooney, David J. .
PHARMACEUTICAL RESEARCH, 2007, 24 (02) :258-264
[9]   TUMOR VASCULAR-PERMEABILITY FACTOR STIMULATES ENDOTHELIAL-CELL GROWTH AND ANGIOGENESIS [J].
CONNOLLY, DT ;
HEUVELMAN, DM ;
NELSON, R ;
OLANDER, JV ;
EPPLEY, BL ;
DELFINO, JJ ;
SIEGEL, NR ;
LEIMGRUBER, RM ;
FEDER, J .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (05) :1470-1478
[10]  
CREASEY AA, 1979, IN VITRO CELL DEV B, V15, P342