Abstract
A tumour invasion model has been developed to examine the influence of diffusible matrix metalloproteinases (MMPs) and the mediated proteolysis of non-diffusible, membrane type MMPs (MT-MMPs) on tumour growth and morphology via haptotaxis. Our results are the first to explore the influence of localized degradation of extracellular matrix (ECM) by MT-MMPs on the morphology of tumours growing in nutrient-rich and nutrient-poor microenvironments. Two-dimensional numerical simulation, using a level-set-based tumour host interface-capturing method, reveals that haptotaxis due to ECM degradation by MMP causes greater instability than with ECM degradation by MT-MMP in low-nutrient environments, even at low proliferation rates; whereas the resulting morphologies are similar for high apoptosis rates. Our simulation results show that while haptotaxis leads to completely different tumour growth rates and morphologies depending on proliferation and apoptosis rates in low-nutrient environment, there are no significant variations when we compare the haptotaxis due to ECM degradation by MMP and MT-MMP, except for low proliferation rates. Focusing on the differences between MMP and MT-MMP mediated effects; our study has important implications in MMP-target validation and MMP-inhibitor-drug development for anti-cancer clinical trials.
Highlights
Tumour invasion is driven by proliferation and migration into the surrounding tissue
We have proposed a two-dimensional continuum model for the growth and invasion of tumour cells into healthy tissue that focuses on four key components implicated in the invasion process: tumour cells, extracellular matrix (ECM), matrix degrading enzymes (MDE) (MMPs or MT-matrix metalloproteinase (MMPs)) and nutrient which are initially homogeneous in the tumour microenvironment
Our model is the first to examine the effect of haptotaxis for localized ECM degradation by membrane type MMPs (MT-MMPs) on tumour growth and morphology in high and low-nutrient environments and differentiate the influences of haptotaxis for various cell proliferation and apoptosis rates in hypoxic environment for soluble and non-soluble MMPs
Summary
Tumour invasion is driven by proliferation and migration into the surrounding tissue. Invasive cells have different characteristics than those of normal cells in that they are less adhesive and more mobile, mitotic, and metabolically active than normal cells [1,2,3,4]. Among these characteristics, cell motility is a crucial aspect of tumour invasion as cells with motile capabilities can access new nutrient sources and infiltrate the surrounding tissue which is essential for metastasis. Chemo taxis is the phenomenon by which the movement of cells is directed in response to a soluble extracellular chemical gradient; i.e., of nutrient or oxygen or other growth factors. The directed movement of cells in response to gradients of fixed or bound (non-diffusible) chemicals, such as the ECM, is known as haptotaxis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Bioengineering & Biomedical Science
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
