The role of the microenvironment in tumor growth and invasion

Abstract

Mathematical modeling and computational analysis are essential for understanding the dynamics of the complex gene networks that control normal development and homeostasis, and can help to understand how circumvention of that control leads to abnormal outcomes such as cancer. Our objectives here are to discuss the different mechanisms by which the local biochemical and mechanical microenvironment, which is comprised of various signaling molecules, cell types and the extracellular matrix (ECM), affects the progression of potentially-cancerous cells, and to present new results on two aspects of these effects. We first deal with the major processes involved in the progression from a normal cell to a cancerous cell at a level accessible to a general scientific readership, and we then outline a number of mathematical and computational issues that arise in cancer modeling. In Section 2 we present results from a model that deals with the effects of the mechanical properties of the environment on tumor growth, and in Section 3 we report results from a model of the signaling pathways and the tumor microenvironment (TME), and how their interactions affect the development of breast cancer. The results emphasize anew the complexities of the interactions within the TME and their effect on tumor growth, and show that tumor progression is not solely determined by the presence of a clone of mutated immortal cells, but rather that it can be ‘community-controlled’. It Takes a Village – Hilary Clinton

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

“…It is known that the interaction between a tumor and its microenvironment plays a large role in tumor development, and a better understanding of this relationship may lead to important new therapeutic approaches for controlling the growth and metastasis of cancer (Kim et al 2011). Several aspects of this interaction have been studied here, and a general theme that emerges is that there are multiple points for intervention in the process beyond simply targeting tumor cells for eradication.…”

“…In the following sections, we analyze the model of the EGF and TGF-β pathways first introduced in Kim et al (2011), hereafter referred to as I. In the third section, we study a 2D hybrid model describing the interactions amongst TECs, fibroblasts, and myofibroblasts via EGF and TGF-β.…”

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

“…Previous mathematical and computational models of DCIS have focused on a single breast duct and have been successful in recapitulating certain features of the spatio-temporal dynamics of proliferating and motile tumor cells at this microscale [18][19][20][21][22][23][24][25][26][27][28][29], and have even, in some cases, been capable of extrapolating their results to predictions of macroscopic growth features [24] or invasive potentials as a function of grade [29]. Here we adopt a multiscale approach to predict growth and size of the volume of breast containing ducts with DCIS based on molecular measurements from histopathology of individual patient tumors.…”

The metastatic microenvironment: Lung‐derived factors control the viability of neuroblastoma lung metastasis

“…1,4-6 As the critical role of the microenvironment in tumor growth and progression is increasingly appreciated, [7][8][9][10][11][12] it has become clear that in order to eliminate metastasis, the full impact of interactions between tumor cells and the microenvironment has to be elucidated. Neuroblastoma, the most common extracranial solid tumor in children, accounts for approximately 15% of all childhood cancer deaths.…”

“…3,4 The ability of dormant tumor cells to "be activated" and subsequently generate a secondary frank metastatic lesion is, to a large extent, a function of their interaction with the microenvironment at the secondary site. 1,[4][5][6] As the critical role of the microenvironment in tumor growth and progression is increasingly appreciated, [7][8][9][10][11][12] it has become clear that in order to eliminate metastasis, the full impact of interactions between tumor cells and the microenvironment has to be elucidated.…”